Significance of radiation therapy in the myxoid round-cell liposarcoma treatment regimen.

BACKGROUND AND PURPOSE: Because myxoid liposarcomas are more radiosensitive than other soft tissue sarcomas, there have been several reports of 50 Gy preoperative radiation therapy combined with surgery, but the wound complication rate is reportedly high. We have performed preoperative irradiation at a reduced dose of 40 Gy and definitive radiation therapy for unresectable cases. This study aimed to report the tumor reduction rate and oncological results with a reduced dose of preoperative irradiation and the outcome of definitive irradiation for unresectable cases. MATERIALS AND METHODS: Forty-one patients with myxoid liposarcoma treated in our institution between 2002 and 2021 were included. We examined the tumor volume shrinkage rate with preoperative radiation, compared complications and oncological outcomes between preoperative radiation and surgery-only cases, and investigated the prognosis and tumor shrinkage of definitive radiation cases. RESULTS: The total dose irradiated was 40 Gy except in two cases. The mean tumor volume reduction rate was 52.0%. A decreased dose of preoperative radiation did not worsen clinical outcomes with fewer complications. The total dose of definitive radiation was approximately 60 Gy. The mean tumor volume reduction rate was 55.0%. The tumor shrinkage maintenance rate was 100% in a median follow-up period of 50.5 months. CONCLUSION: Preoperative radiation therapy for myxoid liposarcoma near vital organs is a good approach because even with a reduced dose of 40 Gy, significant tumor reduction and excellent results were achieved. Definitive radiation therapy is the recommended treatment for older patients with serious comorbidities or inoperable patients.

[Comparative analysis of combined treatment methods for patients with single brain lesions]. / Sravnitel'nyi analiz kombinirovannykh metodov lecheniya patsientov s odinochnym metastaticheskim porazheniem golovnogo mozga.

Primary brain metastases are common in oncology. Preoperative stereotactic radiosurgery followed by surgical resection is a perspective approach. OBJECTIVE: To evaluate own experience of preoperative radiosurgery followed by surgical resection (RS+S) of metastasis regarding local control, leptomeningeal progression, surgical and radiation-induced complications; to compare treatment outcomes with surgical resection and subsequent radiotherapy (S+SRT). MATERIAL AND METHODS. A: Retrospective study included 66 patients with solitary brain metastasis. Two groups of patients were distinguished: group 1 (n=34) - postoperative irradiation, group 2 (n=32) - preoperative irradiation. The median age was 49.5 years (range 36-75). RESULTS: Local 3-, 6- and 12-month control among patients with postoperative irradiation was 88.2%, 79.4% and 42.9%, in the group of preoperative irradiation - 100%, 93.3% and 66.7%, respectively (p=0.021). Leptomeningeal progression developed in 11 patients (8 and 3 ones, respectively). The one-year survival rate was 73.5% and 84.4%, respectively (p=0.33). Long-term surgical and radiation-induced complications occurred in 12 (18.2%) patients. CONCLUSION: Preoperative radiosurgery with subsequent resection provides higher local control and lower incidence of leptomeningeal progression in patients with single brain metastases.

Preoperative Radiation for Soft Tissue Sarcomas: How Much Is Needed?

OPINION STATEMENT: Preoperative radiation therapy is an important component of curative treatment for extremity and superficial trunk soft tissue sarcomas. It has traditionally been delivered to a dose of 50 Gy in 2 Gy fractions over 5 weeks. With significant advances in the multidisciplinary approach to soft tissue sarcomas, preoperative radiation therapy may be omitted for certain cases, delivered over a shortened period of time (1-3 weeks), deintensified for myxoid liposarcomas, or combined with systemic therapy to improve the therapeutic ratio. This article reviews the innovative preoperative radiation therapy strategies currently used to treat extremity and superficial trunk soft tissue sarcomas.

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers.

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

Resection of the irradiated esophagus: the impact of lymph node yield on survival.

There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal (<9) or extensive (≥9) lymph node yield. Demographic, operative, and postoperative outcomes were compared between the groups. Kaplan-Meier analysis with the log rank test was used to compare survival between the yield groups. Cox proportional hazards model was used to determine the association between lymph node yield and survival. In total, 886 cases were included: 349 (39%) belonging to the minimal node group and 537 (61%) to the extensive group. Unadjusted 5-year survival was similar between the minimal and extensive groups, respectively (37.3% vs. 38.8%; P > 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66-0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative.

BACKGROUND AND OBJECTIVES: Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR). METHODS: From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups. RESULTS: LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively). CONCLUSIONS: RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.

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

INTRODUCTION: In 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 METHODS: Approval 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). RESULTS: 90 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). CONCLUSION: Our 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.

Improved local control with an aggressive strategy of preoperative (with or without intraoperative) radiation therapy combined with radical surgical resection for retroperitoneal sarcoma.

BACKGROUND AND OBJECTIVES: We sought to examine our outcomes with advanced preoperative and intraoperative radiation therapy (XRT) combined with aggressive en bloc surgical resection of retroperitoneal sarcoma (RPS) as a strategy to minimize the risk of local recurrence (LR). METHODS: From 2003 to 2013, 46 patients with RPS received preoperative XRT followed by radical en bloc surgical resection, with or without intraoperative electron radiation therapy (IOERT). Clinical and pathologic variables predictive of LR and distant recurrence (DR) were evaluated. RESULTS: Thirty-seven patients had primary tumors and 80% were intermediate grade or higher. All patients received preoperative XRT to a median dose of 50.4 Gy and underwent complete (R0/R1) tumor resection, and 16 patients received IOERT. After a median follow-up of 53 months, 33 (72%) patients were disease-free, and there were 8 (17%) DRs, 2 (4%) abdominal recurrences outside of the XRT field, and 5 (10.9%) LRs. High tumor grade and recurrent disease at presentation were the only factors associated with higher rates of recurrence. CONCLUSIONS: Excellent local control can be achieved with a coordinated strategy of preoperative (±intraoperative) XRT combined with aggressive en bloc surgical resection of RPS, but systemic failure remains a problem for higher-grade tumors.

Agent-based model of epithelial host-pathogen interactions in anastomotic leak.

BACKGROUND: There is a growing recognition of the significance of host-pathogen interactions (HPIs) in gut biology leading to a reassessment of the role of bacteria in intestinal anastomotic leak. Understanding the complexities of the early postsurgical gut HPI requires integrating knowledge of both epithelial and bacterial behaviors to generate hypotheses of potential mechanisms of interaction. Agent-based modeling is a computational method well suited to achieve this goal, and we use an agent-based model (ABM) to examine alterations in the HPI affecting reestablishment of the epithelial barrier that may subsequently lead to anastomotic leak. METHODS: Computational agents representing Pseudomonas aeruginosa were added to a previously validated ABM of epithelial restitution. Simulated experiments were performed examining the effect of radiation on bacterial binding to epithelial cells, plausibility of putative binding targets, and potential mechanisms of epithelial cell killing by virulent bacteria. RESULTS: Simulation experiments incorporating radiation effects on epithelial monolayers produced binding patterns akin to those seen in vitro and suggested that promotility integrin-laminin associations represent potential sites for bacterial binding and disruption of restitution. Simulations of potential mechanisms of epithelial cell killing suggested that an injected cytotoxin was the means by which virulent bacteria produced the tissue destruction needed to generate an anastomotic leak, a mechanism subsequently confirmed with genotyping of the virulent P aeruginosa strain. CONCLUSIONS: This study emphasizes the utility of ABM as an adjunct to traditional research methods and provides insights into the potentially critical role of HPI in the pathogenesis of anastomotic leak.

Effect of pre-operative radiation therapy on surgical outcome in retroperitoneal sarcoma.

Background: A high rate of locoregional recurrence is one of the major difficulties in successful treatment of retroperitoneal sarcoma (RPS). Although pre-operative radiation therapy (RT) is considered a potential way to improve local recurrence, concerns about the associated treatment toxicity and risk of peri-operative complications need to be addressed. Hence, this study investigates the safety of pre-operative RT (preRTx) for RPS. Methods: A cohort of 198 patients with RPS who had undergone both surgery and RT was analyzed for peri-operative complications. They were divided into three groups according to the RT scheme: (1) preRTx group, (2) post-operative RT without tissue expander, and (3) post-operative RT with tissue expander. Results: The preRTx was overall well tolerated and did not affect the R2 resection rate, operative time, and severe post-operative complications. However, the preRTx group was associated with higher incidence of post-operative transfusion and admission to intensive care unit (p = 0.013 and p = 0.036, respectively), where preRTx was an independent risk factor only for the post-operative transfusion (p = 0.009) in multivariate analysis. The median radiation dose was the highest in preRTx group, although no significant difference was demonstrated in overall survival and local recurrence rate. Conclusion: This study suggests that the preRTx does not add significant post-operative morbidity to the patients with RPS. In addition, radiation dose elevation is achievable with the pre-operative RT. However, a meticulous intra-operative bleeding control is recommended in those patients, and further high-quality trials are warranted to evaluate the long-term oncological outcomes.

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma.

Purpose: Recent single institution, phase II evidence has demonstrated the feasibility and efficacy of ultra-hypofractionated, preoperative photon therapy in 5 fractions for the treatment of soft tissue sarcoma (STS). Our purpose was to evaluate the dosimetric benefits of modern scanning beam proton therapy compared with conventional photon radiation therapy (RT) for the neoadjuvant treatment of adult extremity STS. Materials and Methods: Existing proton and photon plans for 11 adult patients with STS of the lower extremities previously treated preoperatively with neoadjuvant RT at our center were used to create proton therapy plans using Raystation Treatment Planning System v10.A. Volumes were delineated, and doses reported consistent with International Commission on Radiation Units and Measurements reports 50, 62, and 78. Target volumes were optimized such that 100% clinical target volume (CTV) was covered by 99% of the prescription dose. The prescribed dose was 30 Gy for PT and RT delivered in 5 fractions. For proton therapy, doses are reported in GyRBE = 1.1 Gy. The constraints for adjacent organs at risk (OARs) within 1 cm of the CTV were the following: femur V30Gy ≤ 50%, joint V30Gy < 50%, femoral head V30Gy ≤ 5 cm3, strip V12 ≤ 10%, and skin V12 < 50%. Target coverage goals, OAR constraints, and integral dose were compared by Student t test with P < .05 significance. Results: A minimum 99% CTV coverage was achieved for all plans. OAR dose constraints were achieved for all proton and photon plans; however, mean doses to the femur (10.7 ± 8.5 vs 16.1 ± 7.7 GyRBE), femoral head (2.0 ± 4.4 vs 3.6 ± 6.4 GyRBE), and proximal joint (1.8 ± 2.4 vs 3.5 ± 4.4 GyRBE) were all significantly lower with PT vs intensity-modulated radiation therapy (IMRT) (all P < .05). Integral dose was significantly reduced for proton vs photon plans. Conformity and heterogeneity indices were significantly better for proton therapy. Conclusion: Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT. Further prospective investigation is warranted to validate these findings and potential benefit in the management of adult STS.

Adjuvant and Neoadjuvant Radiation Therapy for Locally Advanced Bladder Cancer.

Local-regional failure for patients with ≥pT3 urothelial carcinoma after radical cystectomy is a significant clinical challenge. Prospective randomised trials have failed to show that chemotherapy reduces the risk of local-regional recurrences. Salvage treatment for local failures is difficult and often unsuccessful. There is promising evidence, particularly from a recent Egyptian National Cancer Institute trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared with chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the National Comprehensive Cancer Network guidelines were revised to include postoperative radiotherapy as an option to consider for patients with ≥pT3 disease. Here we review the problem of local-regional failure after cystectomy, identify patients who would probably benefit from adjuvant radiotherapy, review the patterns of pelvic failure after cystectomy, discuss technical details of radiation treatment and review the modern literature on this topic. Adjuvant radiotherapy should be considered as a treatment option for patients with locally advanced disease, especially those with positive margins or squamous cell carcinoma.

The role of perioperative ureteral stenting for urologic complications in radical surgery of cervical cancer.

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.

Oncologic outcomes of pre- versus post-operative radiation in Resectable soft tissue sarcoma: a systematic review and meta-analysis.

BACKGROUND: Postoperative radiation therapy for soft tissue sarcomas demonstrated good local recurrence-free survival rates and survival outcomes. However, the results remained controversial. This study aimed to evaluate the role of preoperative and postoperative radiation therapy for the treatment of resectable soft tissue sarcomas. METHODS: The electronic database PubMed, MEDLINE, Cochrane Library, and EMBASE were performed from inception till 30 November, 2019. The effect of preoperative versus postoperative radiation therapy on resectable soft tissue sarcomas was compared and then assessed. RESULTS: A total of 15 studies with 12,813 patients were included, and most of these had acceptable quality scores. Of these, 10 studies reported data on local recurrence. The pooled results indicated no significant differences between preoperative radiotherapy and postoperative radiotherapy groups for local recurrence, with a risk ratio (RR) and 95% confidence interval (CI) of 0.84 (95%CI = 0.58-1.21). No difference was observed in the overall survival and distant metastasis between the two groups. According to the pooled results, preoperative radiotherapy group showed a significant risk for complications (RR = 2.11, 95%CI = 1.36-3.27). CONCLUSIONS: The postoperative radiation therapy does not increase the local recurrence, overall survival, and distant metastasis, but might result in lowering complications.

Use of Preoperative Radiation Therapy in Early-stage and Locally Advanced Breast Cancer.

Purpose There is growing interest in delivering radiation preoperatively (preopRT) rather than postoperatively (postopRT) for breast cancer. Using the National Cancer Database, we evaluated the use and outcomes of preopRT in breast cancer. Methods We identified adult females diagnosed with non-metastatic breast cancer treated with definitive surgery and radiation between 2004 and 2014. Logistic regression models evaluated factors associated with use of preopRT in early-stage (clinical T1-3/N0-1) and locally advanced (clinical T4/N2-3) disease. Rates of breast-conserving surgery, breast reconstruction, positive surgical margins, and 30-day surgical readmissions were compared between patients receiving preopRT and postopRT. Results Of 373,595 patients who met our inclusion criteria, 1,245 (0.3%) patients received preopRT. Patients receiving preopRT were more likely to be of lower socioeconomic status and have tumors with higher T stage. Younger age and N1 (vs N0) disease predicted for use of preopRT in early-stage disease, while older age and N0 disease predicted for use of preopRT in the locally advanced setting. PreopRT patients were less likely to undergo breast-conserving surgery and more likely to have positive surgical margins. Rates of unplanned readmissions within 30 days of surgery were similar among patients treated with preopRT and postopRT. Conclusions PreopRT is a new treatment strategy for patients with breast cancer with different clinical and sociodemographic drivers of its use in the early-stage and locally advanced settings. We await the results of clinical trials studying the efficacy of this approach.

Efficacy of preoperative chemoradiotherapy in downstaging rectal cancer and its impact on the long-term outcome.

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.

Preoperative radiation may improve the outcomes of resectable IIIA/N2 non-small-cell lung cancer patients: A propensity score matching-based analysis from surveillance, epidemiology, and end results database.

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.

Preoperative radiotherapy in breast cancer patients: 32 years of follow-up.

This study evaluates the long-term outcomes of a retrospective cohort of breast cancer (BC) patients who had received curatively intended premastectomy radiation therapy (RT). We analysed locoregional control, disease-free survival (DFS) and overall survival (OS), pathological complete remission (pCR), predictors thereof, and immediate safety. The series consisted of 187 patients with a median age of 49 years [43-60] and T2-T4 or N2 tumours. Between 1970 and 1984, they had received slightly hypofractionated RT to the whole breast, ipsilateral supraclavicular fossa and axilla ± the internal mammary chain (45-55 Gy/18 fractions of 2.5 Gy/34 days) systematically followed by a modified radical mastectomy with an axillary dissection. No other preoperative treatment was given. Among the 166 centrally reviewed tumour biopsy specimens, 22% had a triple-negative (TN) phenotype, 17% were HER2 3 + or amplified and 61% were ER+. The median follow-up was 32 years [23-35]. The 25-year locoregional control rate was 89% [93%-82%] and the 25-year DFS and OS rates were identical, 30% [24%-37%]. A pCR in the tumour and lymph nodes had been achieved in 18 among all patients (10%), but in 26% with TN disease. In the multivariate analysis, the TN status was the only predictive factor of pCR (OR = 5.49, 95% confidence interval [CI] 1.87-16.1, p = 0.002). Also, the pN status (HR = 1.69, [1.28-2.22], p = 0.0002) and TN subtype (HR = 1.80, [1.00-3.26], p = 0.05) exerted a significant prognostic impact on OS. The postoperative complication rate (grade >2) was 19% with 4.3% of localized skin necrosis. Preoperative RT followed by radical surgery is feasible and associated with good long-term locoregional control.