non-IORT Group Research Articles

Outcomes of Intraoperative Radiotherapy for Locally Advanced Adenocarcinoma of the Esophagogastric Junction After Neoadjuvant Therapy: A Single-Arm, Phase 1 Trial Fromthe Chinese National Cancer Center.

The role of intraoperative radiotherapy (IORT) for adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Therefore, a prospective phase 1 trial was conducted to assess the safety and feasibility of IORT for locally advanced AEG. The study enrolled patients with AEG at stages II-IVA from January 2019 to September 2019. Eligible patients received esophagectomy and a single fraction of electron beam radiotherapy. The primary endpoint of the study was a safety profile for IORT. Additionally, survival outcomes and the locoregional recurrence rate (LRR) were compared between the non-IORT and IORT cohorts using propensity score-matching. For 15 (93.8 %) of the 16 patients in the study, R0 resection was successfully achieved, with only one patient undergoing R1 resection. A total postoperative complication morbidity rate of 43.8 % (7/16) was observed, with major complications (Clavien-Dindo classification ≥3) in 12.5 % of the cases (2/16). Total treatment-related adverse events were reported for seven patients (43.8 %, 7/16). After matching, a lower LRR was observed in the IORT group than in the non-IORT group (0 % [0/12] vs 33.3 % [4/12]; p = 0.028). However, the two groups did not differ significantly in 3-year progression-free survival (PFS: IORT [50.9 %] vs non-IORT [53.4 %]; p = 0.93) or 3-year overall survival (OS: IORT [58.3 %] vs IORT [72.9 %]; p = 0.23). The current study demonstrated favorable feasibility and safety of IORT for locally advanced AEG. Although IORT is beneficial for improving local control, it may not prolong PFS or OS for patients with locally advanced AEG. A phase 2 trial is warranted for further validation of these outcomes.

The impact of intraoperative radiotherapy on breast cancer: focus on the levels of angiogenic factors

ObjectiveAngiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients.Patients and methodsThree hundred sixty patients, who had undergone breast-conserving surgery between 2013 and 2018, were enrolled in IORT and non-IORT groups non-randomly. Blood and drained wound fluid (WF) samples were collected from the patients before and after surgery, followed by quantification of the amounts of TGF-β, EGF, FGF, VEGF, and DLL4 in the patients using ELISA.ResultsOur results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4, and VEGF. Furthermore, ROC analyses showed that TGF-β and DLL4 can differentiate of the early-stage from late-stage of the disease. Interestingly, the rate of the death and recurrence was reduced in IORT group.ConclusionsIn summary, IORT is a safe and effective treatment that can affect angiogenic factors and improve the overall- and recurrence-free survival of breast cancer patients.

Role of intraoperative radiotherapy in the treatment of sacral chordoma

Background ContextSacral chordoma is a rare entity with high local recurrence rates when complete resection is not achieved. To date, there are no series available in literature combining surgery and intraoperative radiotherapy (IORT). PurposeThe objective of this study was to report the experience of our center in the management of sacral chordoma combining radical resection with both external radiotherapy and IORT. Study DesignThis is a retrospective case series. Patient SampleThe patient sample included 15 patients with sacral chordoma resected in our center from 1998 to 2015. Outcome MeasuresThe outcome measures were overall survival (OS), disease-free survival (DFS), and rates of local and distant recurrences. MethodsWe retrospectively reviewed the records of all the patients with sacral chordoma resected in our center from 1998 to December 2015. Overall survival, DFS, and rates of local and distant recurrences were calculated. Results between patients treated with or without IORT were compared. ResultsA total of 15 patients were identified: 8 men and 7 women. The median age was 59 years (range 28–77). Intraoperative radiotherapy was applied in nine patients and six were treated with surgical resection without IORT. In 13 patients, we performed the treatment of the primary tumor, and in two patients, we performed the treatment of recurrence disease. A posterior approach was used in four patients. Wide surgical margins (zero residue) were achieved in six patients, marginal margins (microscopic residue) were achieved in seven patients, and there were no patients with intralesional (R2) margins. At a median follow-up of 38 months (range 11–209 months), the 5-year OS in the IORT group was 100% versus 53% in the group of non-IORT (p=.05). The median DFS in the IORT group was 85 months, and that in the non-IORT group was 41 months. In the group without IORT, two patients died and nobody died during the follow-up in the group treated with IORT. High–sacrectomy treated patients had a median survival of 41 months, and low–sacrectomy treated patients had a median survival of 90 months. Disease-free survival in patients without gluteal involvement was 100% at 5 years, and that in patients with gluteal involvement was 40%. All patients with a recurrence in our study had gluteal involvement. ConclusionsMultidisciplinary management of sacral chordoma seems to improve local control. The use of IORT, in our experience, is associated with an increase in OS and DFS. The level of resection and gluteal involvement seems to affect survival. The posterior approach is useful in selected cases. Multicenter studies should be performed to confirm the utility of IORT.

Efficacy of intraoperative radiotherapy targeted to the abdominal lymph node area in patients with esophageal carcinoma

We investigated whether intraoperative radiotherapy (IORT) during curative surgery for esophageal carcinoma is useful or not. The cases of 117 patients diagnosed with thoracoabdominal esophageal carcinoma who underwent curative surgery between 1986 and 2007 were reviewed: 72 patients received IORT (IORT group) and 45 did not (non-IORT group). Upper abdominal lymphadenectomy was performed in 115 patients (98.5%). Seventy patients (59.8%) received chemotherapy and 80 patients (68.4%) received external radiotherapy. IORT encompassed the upper abdominal lymph node area. A single-fraction dose of 20–30 Gy was delivered using high-energy electrons. Median follow-up duration for patients was 7.4 years. The 5-year overall survival rate did not significantly differ between the IORT and non-IORT groups. However, the 5-year abdominal control rate was significantly higher in the IORT group (89.2%) than in the non-IORT group (72.9%; P = 0.022). We next focused on a patient subgroup with a primary lesion in the lower thoracic or abdominal esophagus or measuring >6 cm in length since this subgroup is probably at high risk of upper abdominal lymph node metastasis. Of the 117 patients, 75 belonged to this subgroup, and among them 45 received IORT. Both univariate and multivariate analysis revealed the survival rate was significantly higher in patients who received IORT than in those who did not (P = 0.033 univariate; 0.026 multivariate). There were no obvious perioperative complications solely attributed to IORT. IORT for esophageal carcinoma will likely be effective for patients with a primary lesion in the lower thoracic or abdominal esophagus, or with a long lesion.

Does Intraoperative Radiation Therapy Improve Local Tumor Control in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Adenocarcinoma? A Propensity Score Analysis

Locoregional recurrence (LRR) is an important factor after pancreaticoduodenectomy (PD) for pancreatic cancer. Intraoperative radiation therapy (IORT) administered to the resection bed may improve local tumor control. We performed a retrospective analysis of patients who underwent PD at Thomas Jefferson University Hospital (TJUH) between 1995 and 2005 to identify patients who underwent resection with and without IORT. Data collected included age, gender, complications, margin status, stage, survival, and recurrence. Unadjusted analyses of the IORT and non-IORT groups were performed using Fisher's chi-square method for discrete variables and Wilcoxon rank sum test for continuous variables. To account for biases in patient selection for IORT, a propensity score was calculated for each patient and adjusted statistical analyses were performed for survival and recurrence outcomes. Between January 1995 and November 2005, 122 patients underwent PD for periampullary tumors, including 99 pancreatic cancers. Of this group, 37 patients were treated with IORT, and there was adequate follow-up information for a group of 46 patients who underwent PD without IORT. The IORT group contained a higher percentage of Stage IIB or higher tumors (65%) than in the non-IORT group (39.1%), though differences in stage did not reach significance (P = .16). There was a nonsignificant decrease in the rate of LRR in patients who had IORT (39% non-IORT vs. 23% IORT, P = .19). The median survival time of patients who received IORT was 19.2 months, which was not significantly different than patients managed without IORT, 21.0 months (P = .78). In the propensity analyses, IORT did not significantly influence survival or recurrence after PD. IORT can be safely added to management approaches for resectable pancreatic cancer, with acceptable morbidity and mortality. IORT did not improve locoregional control and did not alter survival for patients with resected pancreatic cancer. IORT is an optional component of adjuvant chemoradiation for pancreatic cancer. In the future, IORT may be combined with novel therapeutic agents in the setting of a clinical trial in order to attempt to improve outcomes for patients with pancreatic cancer.

Does Intraoperative Radiation Therapy Improve Local Tumor Control in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Adenocarcinoma? A Propensity Score Analysis

Background: Locoregional recurrence (LRR) is an important factor after pancreaticoduodenectomy (PD) for pancreatic cancer. IORT administered to the resection bed may improve local tumor control. Methods: We performed a retrospective analysis of patients who underwent PD at Thomas Jefferson University Hospital (TJUH) between 1995 and 2005 to identify patients who underwent resection with and without intraoperative radiation therapy (IORT). Data collected included age, gender, complications, margin status, stage, survival, and recurrence. Unadjusted analyses of the IORT and non-IORT groups were performed using Fisher’s chi-square method for discrete variables and Wilcoxon Rank Sum test for continuous variables. To account for biases in patient selection for IORT, a propensity score was calculated for each patient and adjusted statistical analyses were performed for survival and recurrence outcomes. Results: Between January 1995 and November 2005, 122 patients underwent PD for perimpullary tumors, including 99 pancreatic cancers. Of this group, 37 patients were treated with IORT, and there was adequate follow-up information for a group of 46 patients who underwent PD without IORT. The IORT group contained a higher percentage of Stage IIB or higher tumors (65%) than in the non-IORT group (39.1%), though differences in stage did not reach significance (p = 0.16). There was a non-significant decrease in the rate of LRR in patients who had IORT (39% non-IORT vs. 23% IORT, p = 0.19). The median survival time of patients who received IORT was 19.2 months, which was not significantly different than patients managed without IORT, 21.0 months (p=0.78). In the propensity analyses, IORT did not significantly influence survival or recurrence after PD. Conclusions: IORT can be safely added to management approaches for resectable pancreatic cancer, with acceptable morbidity and mortality. IORT did not improve loco-regional control and did not alter survival for patients with resected pancreatic cancer. IORT is an optional component of adjuvant chemoradiation for pancreatic cancer. In the future, IORT may be combined with novel therapeutic agents in the setting of a clinical trial in order to attempt to improve outcomes for patients with pancreatic cancer. Annals of Surgical Oncology, Volume 16, Edition 8, August, 2009, pages 2116-22, “Does intraoperative radiation therapy improve local tumor control in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma? A propensity score analysis”. Authors: Showalter TN, Rao AS, Anné PR, Rosato FE, Rosato EL, Andrel J, Hyslop T, Xu X, Berger AC.

Preoperative irradiation and surgery for recurrent rectal cancer. Will intraoperative radiotherapy (IORT) be of additional benefit? A prospective study

Background: The therapeutic gain of surgery for recurrent rectal cancer is not clear, particularly with regard to the addition of intraoperative radiotherapy (IORT). Methods: Patients (107) with isolated pelvic recurrence of rectal cancer received preoperative external radiotherapy of 46–50 in 2 Gy fractions. At surgery 59 patients had IORT 12–18 Gy. Survival and local recurrence was analysed with regard to surgical resection stages and IORT. Results: Patients (44) had R0- and 39 R1-resections, 24 R2-resections or exploratory laparotomy. IORT was given most often after R1-resections, least in R0-patients. Estimated 5-year survival was overall around 30%, around 60% in the R0-, around 25% for R1- and 0% in R2-patients. Local recurrence was around 30% in the R0- and around 65% in R1-stage patients. R0-/R1-stage patients survived statistically significantly longer than the R2-group otherwise there was no statistical significant difference between IORT and non-IORT groups in any R-stages regarding overall survival or local recurrence. Conclusions: Macroscopic removal of the recurrence improves survival. Whether R0- is better than R1-resections is not clear. The effect of IORT is not a major one. IORT need be evaluated in randomised controlled trials.

Intra-operative irradiation (IORT) for primary advanced and recurrent rectal cancer: a need for randomised studies

The aim of this study was to determine the impact of intra-operative irradiation (IORT) combined with pre-operative external beam irradiation (EBRT) and surgical resection in patients with locally advanced primary or recurrent rectal cancer. 64 patients with locally advanced primary cancer and 104 with recurrence had EBRT (46–50 Gy) before surgery. 80 patients received IORT (median dose 15 Gy energy 12 MeV). 80 patients had R0 resections, 47 R1 and 41 R2 resections. More R1 resections were performed in the IORT group, more R0 and R2 resections in the non-IORT group. Median follow-up was around 22 months. 146 patients were resected, 22 had exploratory laparotomy. The cumulative overall survival was similar for both the IORT and non-IORT groups. 5-year survival for primary cancers was 48% versus 28% for recurrences. No R2 resections survived 3.5 years. 5-year-survival for R0 resections was nearly 60% and around 30% for R1 resections. The survival curves of the patients given and not given IORT treatment was not statistically different when R0, R1 and R2 resections were analysed separately. IORT did not seem to influence the local recurrence rate when R0 and R1 resections were analysed separately or in a multivariate analysis. The IORT and non-IORT groups were not identical with regard to type of cancer and R-stage. Still the lack of an identifiable impact of IORT suggests that there is a need for randomised studies of the IORT effect.

Intraoperative and postoperative radiotherapy in pancreatic cancer.

In the 1985-1994 period, 101 patients underwent resection for ductal pancreatic adenocarcinoma. In 27 patients, the resection was not associated with adjuvant therapies, whereas in 74 patients, it was. Intraoperative radiation therapy (IORT) was performed in 54 patients. Operative mortality and morbidity were similar in patients undergoing IORT (1.8 and 29.6%) to those undergoing resection alone (2.1 and 27.6%). Median survival of the IORT group was 17 vs 14 mo of the non-IORT group (irrespective of postoperative treatments) (ns); the local recurrence rates were 38 and 54%, respectively. The group of 74 patients undergoing adjuvant therapies had a greater survival than 27 patients with no adjuvant treatment, both at the univariate (p < 0.01) and the multivariate analyses (p < 0.05) (covariates tumor stage and radicality). The subgroup of patients undergoing only radiotherapy (RT) and/or chemotherapy (CT) did not show significantly better survival than patients with no additional therapies, whereas the group of patients undergoing IORT + CT + RT showed a significantly better survival (p < 0.05). In conclusion, adjuvant therapies seem to improve survival in patients undergoing resection for pancreatic cancer.

Intraoperative radiotherapy for resectable and unresectable pancreatic carcinoma

Eighty patients with pancreatic carcinoma were treated by intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of 111 patients treated by surgery alone. For resectable patients, the radiation dose was 30 Gy and the average field sizes were 8 or 10 cm; for unresectable patients, these values were 20–30 Gy and 6 or 8 cm, respectively. No side effects of IORT were observed. In 49 resectable stage III patients, the IORT group (n=16) had a higher survival rate than the non-IORT group (n=33); i.e., 1-year survival rates of 44.6% vs 23% and 2-year survival rates of 37.2% vs 7.7% after surgery (P<0.05). However, there was no significant difference in survival rate between the IORT group (n=28) and the non-IORT group (n=29) in 57 resectable patients in stage IV. In unresectable patients, the IORT group (n=31) (P<0.05) had a higher survival rate than the non-IORT group (n=38) (P<0.05). The palliative effect of IORT on abdominal or back pain was evaluated in 15 patients who had such symptoms and did not undergo tumor resection. Overall, pain decreased or disappeared in 13 of these patients (87%).