Moderate dose intraoperative and external beam radiotherapy for locally recurrent rectal carcinoma.

BACKGROUND AND PURPOSE: Late adverse effects (i.e. neuropathy, chronic bowel obstruction) limit the effective dose given in intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). Initial results of a multi-modality treatment approach using moderate dose IORT and moderate dose EBRT are presented. PATIENTS AND METHODS: Thirty-one consecutive patients with recurrent rectal carcinomas had IORT and EBRT after complete (R0, n = 14) or incomplete resection (R1, n = 9; R2, n = 8). The mean [ORT dose was 13.7 Gy (range 12-20 Gy) supplemented with an EBRT dose of 41.4 Gy. Twenty-two patients had preoperative EBRT and 22 patients had concomitant chemotherapy (5-FU, Leucovorine). RESULTS: After a median follow-up of 28 months, 16 patients had re-recurrent disease and 11 patients had died. Nine patients failed locally (four in-field, four marginal and one anastomotic re-recurrence), three combined with distant metastasis, resulting in overall and IORT infield local control rates of 71% and 87%, respectively. Distant metastases alone were found in seven patients. The 4-year overall and relapse-free survival rates were 58% and 48%, respectively. After incomplete resection the local failure rate increased (R0 21%, R1/2 35%) and the 4-year relapse-free survival rate decreased significantly (29% versus 71%) due to a markedly increased distant metastasis rate (53% versus 7%). Acute and late toxicities were not increased. CONCLUSION: The combination of moderate dose IORT and EBRT is a safe and efficacious component in a multi-modality treatment approach.     

软组织肉瘤手术加术中放疗的临床研究

目的:探讨软组织肉瘤术中放疗的意义。方法:对39例软组织肉瘤患者行根治或姑息性手术,术中放疗在术中放疗手术室进行,术中根据肿瘤大小,选择不同术中放疗限光筒及6～12MeV电子线1次照射15～25Gy,姑息手术者剂量加大至36Gy。术后辅以外照射治疗,常规设野,5/周,2Gy/次,总量40～50Gy。初发病灶10例,术后复发29例。结果:39例患者随访12～64个月,3、5年局控率分别为71.8%和64.1%。3年生存率为82.0%。结论:术中放疗具有较高的局控率,比之其他治疗具有许多优点,将获得较高的生存率。     

Management of soft tissue sarcomas in first isolated local recurrence: a retrospective study of 83 cases]

PURPOSE: To analyse the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcoma (trunk or extremities) and to identify prognosis factors. PATIENTS AND MATERIAL: This is a retrospective study of 83 adult patients treated between 1980 and 1999. Mean tumor size was 6 cm. Most sarcomas were located in extremities (N =74), were deep (N =60), and proximal (N =53). Thirty involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (32 cases), marginal resection (46 cases), five patients requiring amputation. Final results were R0 (N =33), R1 (N =47) or R2 (N =3) resection. Beside surgery, six patients received neoadjuvant and seven others adjuvant chemotherapy. Twenty-three patients received postoperative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial (192)Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 59 months. Thirty-seven (45%) tumors relapsed, 62% locally as first event. Nineteen patients developed secondary distant metastases. Multivariate analysis showed only tumour depth (P =0.05) and re-resection for primary R1 resection for the recurrence (P =0.018) being independent prognosis factors for tumour control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P =0.05). Overall survival rate was 73, 54, and 47% at respectively 3, 5 and 10 years, and was 65, 35 and 32% after a further local recurrence. Multivariate analysis showed trunk (P =0.0001) or inferior extremity locations (P =0.023), symptomatic (P =0.001), high grade (P =0.01), deep (P = 0.01) tumours, and the occurrence of a further local failure (P =0.004) as unfavourable characteristics for overall survival. CONCLUSION: Because of the high relapse rate in this series, a first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment for the first local relapse is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, brachytherapy being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumours, at best performed in centers that have expertise in this field.     

Pattern of failures in gastric cancer patients with lymph node involvement treated by surgery, intraoperative and external beam radiotherapy.

AIMS: High local failure rates in gastric cancer have been reported, up to 67%. To achieve a better local control, we evaluated intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) in association with surgery for gastric cancer patients with lymph node involvement. We report here the analysis of the patterns of failure for patients involved in this IORT protocol. MATERIAL AND METHODS: Forty-two positive lymph node (N+) gastric cancer patients were operated on (31 total, three subtotal and eight extended gastrectomies) with IORT procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years). IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in 36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients. RESULTS: One patient died postoperatively. Actuarial pN+ 10 year survival rate was 44.8%. The 5 year actuarial local control and disease-free survival rates were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5 patients have a local coeliac recurrence (12%) and 12 have distant metastases with no evidence of coeliac recurrence. CONCLUSION: This retrospective analysis suggests a potential effect of IORT and/or EBRT in promoting local control and long-term survival in gastric cancer patients with lymph node involvement.     

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.     

The script concordance test in radiation oncology: validation study of a new tool to assess clinical reasoning

Purpose

To retrospectively evaluate the results after a regimen of surgery, IORT (intraoperative radiotherapy), and EBRT (external beam radiotherapy) for soft-tissue sarcomas

Methods

38 consecutive patients underwent IORT for soft-tissue sarcoma; 29 were treated for primary tumours, 9 for recurrences. There were 14 cases with liposarcomas, 8 with leiomyosarcomas, 7 with malignant fibrous histiocytomas. 27/38 tumours were located in the extremities, the remaining ones in the retroperitoneum or the chest. Radical resection was attempted in all patients; a R0-resection was achieved in 15/38 patients, R1 in 12/38 pats and R2 in 4/38 pats. IORT was performed using a J-125 source and a HDR (high dose rate) afterloading machine after suturing silicone flaps to the tumour bed. The total dose applied ranged from 8–15 Gy/0.5 cm tissue depth measured from the flap surface. After wound healing external beam radiotherapy (EBRT) was applied in 31/38 patients with total doses of 23–56 Gy dependent on resection status and wound situation. The mean duration of follow-up was 2.3 years.

Results

A local recurrence was found in 10/36 patients, lymph node metastases in 2/35, and distant metastases in 6/35 patients. The actuarial local control rate was 63%/5 years. The overall survival rate was 57%/5 years. There was no statistically significant difference between the results after treatment for primaries or for recurrences. Late toxicity to the skin was found in 13/31 patients, wound healing problems in 5/31 patients. A neuropathy was never seen.

Conclusion

The combination of surgery, IORT, and EBRT yields favourable local control and survival data which are well within the range of the results reported in the literature. The complication rates, however, are considerable although the complications are not severe, they should be taken into account when therapy decisions are made.     

High-dose intraoperative radiotherapy for unresectable pancreatic cancer

PURPOSE: The results of high-dose intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for unresectable pancreatic cancer were analyzed to evaluate the possible advantages of IORT in combination with EBRT. METHODS AND MATERIALS: Between 1983 and 1993, 115 patients with unresectable adenocarcinoma of the pancreas (53 with non-Stage IV disease and 62 with Stage IV disease) were treated with EBRT + IORT (55 patients), EBRT alone (44 patients), or IORT alone (16 patients). In non-Stage IV patients, the use of EBRT alone was due to the unavailability of IORT and the use of IORT alone was due to refusal of EBRT. The IORT dose was 30-33 Gy and the EBRT dose was 40-60 Gy. A historical control group comprised of 101 patients undergoing palliative surgery alone was also analyzed. RESULTS: Both non-Stage IV and Stage IV patients receiving EBRT with or without IORT had a better prognosis than the nonirradiated historical controls. Among non-Stage IV patients, the median survival of the EBRT + IORT group (8.5 months) and the EBRT group (8 months) was similar, although survival from 12 to 18 months was higher in the former group (38% vs. 10% at 12 months, p = 0.018, and 19% vs. 0% at 18 months, p = 0.023). In Stage IV patients, the prognosis was not influenced by the type of radiotherapy. Multivariate analysis revealed that a pretreatment carbohydrate antigen (CA) 19-9 level < 1000 U/ml was associated with better survival. In non-Stage IV patients with a CA 19-9 level < 1000 U/ ml, EBRT + IORT appeared to produce a better survival than EBRT alone (p = 0.047). This was supported by multivariate analysis. CONCLUSION: High-dose IORT + EBRT may be more effective than EBRT alone in patients with unresectable but localized pancreatic cancer and a low CA 19-9 level.     

A study of radiotherapy modalities combined with continuous 5-FU infusion for locally advanced gastrointestinal malignancies.

AIM: We describe the feasibility of combining infusional 5-fluorouracil (5-FU) with intraoperative radiation therapy (IORT). METHODS: Patients with surgically resectable locally advanced gastrointestinal cancers were treated concurrently during surgery with IORT and a 72 h infusion of 5-FU. Patients without previous external beam radiation therapy (EBRT) were subsequently treated with EBRT (40-50Gy) concurrent with a 21-day continuous infusion of 5-FU. Pancreatic, gastric, duodenal, ampullary, recurrent colorectal, and recurrent anal cancer were included. RESULTS: During IORT/5-FU, no chemotherapy-related grade III or IV hematologic or gastrointestinal toxicity was noted. Post-surgical recovery or wound healing was not affected. One of nine patients who received post-operative radiation required a treatment break. During follow-up, there were more complications in patients with pelvic tumours, especially those with previous radiation. Nine patients have had local and/or local regional recurrences, two of these in the IORT field. CONCLUSIONS: Treatment with a combination of IORT and 5-FU followed by EBRT and 5-FU is feasible. However, long-term complications may be increased in previously irradiated recurrent pelvic tumours.     

Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer

PURPOSE: To determine the survival of pancreatic cancer patients treated with intraoperative radiotherapy (IORT) and/or external beam radiation therapy (EBRT) following macroscopically curative resection. METHODS AND MATERIALS: One hundred and thirty-eight patients with pancreatic cancer who had undergone potentially curative total or regional pancreatectomy between 1980 and 1997 were retrospectively analyzed. Among the 138 patients, 98 had a pathologically negative surgical margin and the remaining 40 patients had a positive surgical margin. The usual EBRT dose was 45-55 Gy with a daily fraction of 1.5-2.0 Gy. The median IORT dose was 25 Gy in a single fraction. RESULTS: The 2-year cause-specific survival rate of patients with pathologically negative surgical margins was 19%, and that of patients with positive margins was 4% (p < 0.005). Although the median survival time (MST) of patients with negative margins treated with IORT and EBRT was significantly longer than that of those treated with operation alone (17 vs. 11 months), no significant difference in survival curves was observed. In patients with positive surgical margins in peripancreatic soft tissue, the difference between the survival curve of patients treated with surgery alone and that of those treated with surgery and radiation therapy was borderline significant (p < 0.10). Patients receiving intraarterial or intraportal infusion chemotherapy had significantly improved survival rates compared with those who did not receive it (p < 0.05). CONCLUSION: Although the MST was longer in patients with negative margins receiving IORT and EBRT than in those receiving no radiation, improved long-term survival by IORT and/or EBRT was not suggested. In patients with positive margins, our results obtained by IORT/EBRT were encouraging. Randomized studies with much higher patient numbers are necessary to define the role of IORT in curatively resected pancreatic cancer.     

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.     

Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system

INTRODUCTION: Intraoperative radiotherapy (IORT) with low-energy X-rays (30-50 KV) is an innovative technique that can be used both for accelerated partial breast irradiation (APBI) and intraoperative boosting in patients affected by breast cancer. Immediately after tumor resection the tumor bed can be treated with low-distance X-rays by a single high dose. Whereas often a geographic miss in covering the boost target occurs with external beam boost radiotherapy (EBRT), the purpose of IORT is to cover the tumor bed safely. This report will focus on the feasibility and technical aspects of the Intrabeam device and will summarize our experience with side effects and local control. MATERIALS AND METHODS: Between February 2002 and June 2003 57 breast cancer patients, all eligible for breast conserving surgery (BCS), were treated at the Mannheim Medical Center with IORT using the mobile X-ray system Intrabeam. The patient population in this feasibility study was not homogeneous consisting of 49 patients with primary stage I or II breast cancer, seven with local recurrence after previous EBRT and one with a second primary in a previously irradiated breast. The selection criteria for referral for IORT included tumor size, tumor cavity size, margin status and absence of an extensive intraductal component. The previously irradiated patients with local recurrences and 16 others received IORT as single modality. In all other cases IORT was followed by EBRT with a total dose of 46 Gy in 2-Gy fractions. The intraoperatively delivered dose after tumor resection was 20 Gy prescribed to the applicator surface. EBRT was delivered with a standard two-tangential-field technique using linear accelerators with 6- or 18-MV photons. Patients were assessed every three months by their radiation oncologist or surgeon during the first year after treatment and every six months thereafter. Breast ultrasound for follow-up was done every six months and mammographies once yearly. Acute side effects were scored according to the CTC/EORTC score and late side effects according to the Lent-Soma classification. RESULTS: Twenty-four patients received IORT only; eight patients because they had received previous radiotherapy, 16 because of a very favorable risk profile or their own preference. Thirty-three patients with tumor sizes between 1 and 30 mm and no risk factors were treated by IORT as a boost followed by EBRT. The Intrabeam system was used for IORT. The Intrabeam source produces 30-50 KV X-rays and the prescribed dose is delivered in an isotropic dose distribution around spherical applicators. Treatment time ranged between 20 and 48 minutes. No severe acute side effects or complications were observed during the first postoperative days or after 12 months. One local recurrence occurred 10 months after surgery plus IORT followed by EBRT. In two patients distant metastases were diagnosed shortly after BCS. DISCUSSION: IORT with the Intrabeam system is a feasible method to deliver a single high radiation dose to breast cancer patients. As a preliminary boost it has the advantage of reducing the EBRT course by 1.5 weeks, and as APBI it might be a promising tool for patients with a low risk of recurrence. The treatment is well tolerated and does not cause greater damage than the expected late reaction in normal tissue.     

Intraoperative radiation therapy for patients with recurrent rectal and sigmoid colon cancer in previously irradiated fields.

A retrospective study evaluated 15 patients with pelvic recurrence of colorectal cancer in a previously irradiated region who received intraoperative radiation therapy (IORT) as part of salvage therapy. Total prior external beam radiation therapy (EBRT) doses ranged from 45 to 79.2 Gy. Tumor resection was accomplished in 14 patients, with an exenteration performed in seven. IORT dose was 15-20 Gy. Three patients received additional EBRT as a post-operative course of 25.2 Gy in 14 fractions. Actuarial 3-year local control rate was 25%. The 3-year overall survival rate was 29%. Patients with fixed and/or bulky pelvic tumors had a local control rate of 19% at 12 months and median overall survival of 9 months. Patients with less extensive clinical presentations of anastomotic non-fixed transmural recurrence, isolated pelvic node metastasis and rectal recurrence following local excision had a local control rate of 42% at 36 months and median survival of 43 months. We conclude that clinical presentation of recurrent disease is an important prognostic factor. The value of IORT may be limited to patients with less extensive clinical presentations.     

Management of soft tissue sarcomas (STS) in first isolated local recurrence: a retrospective study of 83 cases.

PURPOSE: To analyze the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcomas (trunk or extremities) and to identify prognosis factors. METHODS AND MATERIAL: Between 1980 and 1999, 83 adult patients were included in the study. Mean age was 61 years. Mean tumor size was 6 cm. Most sarcomas were located in extremities (n=74), were deep (n=60), and proximal (n=53); 30 involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histiocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (29 cases), marginal resection (43 cases), 5 patients requiring amputation. Final results were R0 (n=33), R1 (n=47) or R2 (n=3) resection. Besides surgery, 6 patients received neo-adjuvant and 7 others adjuvant chemotherapy. Twenty three patients received post-operative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial 192Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 13 years. Thirty-seven (45%) patients relapsed, 62% of whom presenting an isolated local recurrence. Nineteen patients developed distant metastases. Multivariate analysis showed only tumor depth (P=0.05) and re-resection for primary R1 resection (P=0.018) being independent prognosis factors for tumor control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P=0.05). Overall survival rate was 73%, 54%, and 47% at, respectively, 3.5 and 10 years, and was 65%, 35% and 32% after a further local recurrence. Multivariate analysis showed trunk (P=0.0001) or inferior extremity locations (P=0.023), symptomatic (P=0.001), high grade (P=0.01), deep (P=0.01) tumors, and the occurrence of a further local failure (P=0.004) as unfavorable characteristics for overall survival. CONCLUSIONS: A first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, BCT being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumors, at best performed in centers that have expertise in this field.     

Ic期子宫内膜癌患者中MPA和EBRT的联合疗效

Objective: To report the comparative effect of combined medroxyprogesterone acetate (MPA) and external beam pelvic radiotherapy (EBRT) with EBRT alone on local or distant recurrences, overall survival and treatment related toxicities in patients with stage Ic grade 3 endometrial cancer. Methods: A retrospective review of 80 International Federation of Gyne-cology and Obstetrics (FIGO) stage Ic grade 3 endometrial carcinoma patients treated between October 1994 and October 2004 at Renmin Hospital, Wuhan University, China was performed. All patients underwent surgery, of which 40 patients in arm I received combined MPA and EBRT while in arm II 40 patients received only adjuvant EBRT after surgery. The median dose of EBRT in arm I was 50 Gy (range 36-54 Gy) and in arm II was 45.2 Gy (range 43.2-50.4 Gy). Multivariate analysis was performed for the prognostic factors and Kaplan-Meier method was used for overall survival. Results: Of the 80 eligible patients, 40 in each group could be evaluated. The follow-up times ranged from 4-98 months with a median of 45 months. The overall survival rates at five years were 73% among patients treated with combined MPA and EBRT and 28.2% among patients treated with EBRT alone (P < 0.001). The rate of distant metastasis was significantly higher among patients treated with EBRT alone group than combined MPA and EBRT (55% vs 25%, P = 0.006) while no difference in loco regional recur-rence rates was observed in both treatment groups. Most of the side effects observed in the combined MPA and EBRT group. Age (P < 0.001) and the presence of progesterone receptors (P = 0.003) were independent significant prognostic factors for overall survival in multiple regression analysis. Conclusion: We has been concluded that the addition of progestagen to external beam pelvic radiotherapy significantly improved survival and reduced distant metastasis among women with stage Ic grade 3 endometrial cancer.     

Recurrent endometrial cancer after surgery alone: results of salvage radiotherapy

PURPOSE: Postoperative irradiation of endometrial cancer patients decreases the risk of local recurrence but is associated with a number of long-term sequelae. In a proportion of patients, no immediate postoperative radiotherapy is applied and this treatment is introduced only at relapse. The aim of our study was to assess the long-term results of salvage radiotherapy in previously nonirradiated endometrial cancer patients who developed local recurrence, and to evaluate the impact of patient- and treatment-related factors on treatment efficacy. METHODS AND MATERIALS: We performed a detailed retrospective analysis of 73 endometrial cancer patients given radiotherapy for local recurrence after the initial surgery only. The mean age at diagnosis of the recurrence was 63 years (range, 39-78 years). Median time to recurrence was 11 months (range, 1-19 months). All recurrences were staged with the use of Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma. There were five (7%) Stage I patients, 43 (59%) Stage II patients, and 25 (34%) Stage III patients. Forty-four patients (60%) received both external beam irradiation (EBRT) and endovaginal brachytherapy (BRT), 17 (23%) received only BRT, and 12 (17%) received only EBRT. The mean total physical radiation dose was 75.9 Gy (range, 8-130 Gy), and the mean normalized total dose (NTD) calculated on the base of the linear-quadratic model was 86.6 Gy (range, 8.5-171.9 Gy). Median follow-up for alive patients was 8.8 years (range, 3-21 years). The impact of patient-, tumor-, and therapy-related factors on the treatment outcome was evaluated with the use of uni- and multivariate analyses. RESULTS: Three- and 5-year overall survival rates were 33% and 25%, respectively. In the univariate analysis, lower stage of recurrent disease (p < 0.0005), combined EBRT and BRT (p = 0.027), higher total radiation dose (p = 0.031), and higher NTD (p = 0.006) were significantly correlated with better survival. In the multivariate analysis, only stage of recurrent disease (p < 0.005) and high total dose (p = 0.047) were independently correlated with better survival. Lower FIGO stage of recurrence (p = 0.023) and higher total dose (p = 0.005) were also independently correlated with longer time to progression, whereas higher radiotherapy dose was the only factor correlated with better local control (p = 0.029). CONCLUSIONS: The efficacy of salvage radiotherapy in endometrial cancer patients with local failure after previous surgery is limited. Factors determining treatment outcome include advancement of the tumor at relapse and radiotherapy dose.     

External Beam Radiotherapy in the Treatment of Gastroenteropancreatic Neuroendocrine Tumours: A Systematic Review

Aims

External beam radiotherapy (EBRT) is infrequently used to treat gastroenteropancreatic neuroendocrine tumours (GEPNETS), with little published data to date. We carried out a systematic review to assess the activity of EBRT for GEPNETS.

Intraoperative radiotherapy for recurrent and/or residual colorectal cancer

Intraoperative radiotherapy (IORT) is an attractive boosting modality in the combined treatment of recurrent and/or residual colorectal cancer. Twenty seven patients treated with IORT are analysed. Residual disease following resection of the primary tumor was treated in 11 cases (group I). Localized recurrent disease without previous radiotherapy was treated in 11 cases (group II). IORT was used in five additional patients with local recurrences in previously irradiated areas (group III). The treatment program consisted of maximal tumor resection, IORT (10-30 Gy) to the area of residual disease and external beam radiotherapy (46-50 Gy). The median follow-up time for the entire series of patients is 11 months. Local tumor control rates are 90% in group I, 63% in group II and 60% in group III. Toxicity and complications related to IORT observed in this initial experience have been pelvic pain (29%) and lower extremity neuropathy (3%). These early clinical results suggest that the IORT combined with surgery and external beam radiotherapy is feasible in primary and recurrent disease. Local control rates obtained in patients not suitable for curative surgery are encouraging.     

Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment

PURPOSE: To evaluate the clinical outcomes of patients with localized retroperitoneal soft tissue sarcoma (STS) treated with complete surgical resection and radiation. METHODS AND MATERIALS: The medical records of 83 patients were reviewed retrospectively. Sixty patients presented with primary disease and the remaining 23 had recurrence after previous surgical resection. RESULTS: With a median follow-up of 47 months, the actuarial overall disease-specific survival (DSS), distant metastasis-free survival, and local control (LC) rates were 44%, 67%, and 40%, respectively. Of the 38 patients dying of disease, local disease progression was the sole site of recurrence for 16 patients and was a component of progression for another 11 patients. Multivariate analysis indicated that histologic grade was associated with the 5-year rates of DSS (low-grade, 92%; intermediate-grade, 51%; and high-grade, 41%, p = 0.006). Multivariate analysis also indicated an inferior 5-year LC rate for patients presenting with recurrent disease, positive or uncertain resection margins, and age greater than 65 years. The data did not suggest an improved local control with higher doses of external-beam radiation (EBRT) or with the specific use of intraoperative radiotherapy (IORT). Radiation-related complications (10% at 5 years) developed in 5 patients; all had received their EBRT postoperatively. CONCLUSIONS: Although preoperative radiation therapy and aggressive surgical resection is well tolerated in patients, local disease progression continues to be a significant component of disease death. In this small cohort of patients, the use of higher doses of EBRT or IORT did not result in clinically apparent improvements in outcomes.     

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.     

High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer

PURPOSE: Management of locally recurrent colorectal adenocarcinoma represents a significant challenge. Many of these tumors adhere to or invade into vital pelvic structures rendering surgery or external beam radiotherapy (EBRT) as palliative treatment. Therefore, a treatment approach was developed to evaluate the role of high-dose-rate intraoperative brachytherapy (HDR-IORT) and surgery as a component of therapy in the management of locally recurrent colorectal cancer. This is an update of our preliminary report with longer follow-up and larger patient numbers. METHODS AND MATERIALS: Between January 1992 and September 1998, 74 patients with locally recurrent rectal cancer were treated with surgery and HDR-IORT. Additional EBRT was given to 29 patients, and 33 patients received 5-fluorouracil based chemotherapy. All patients underwent complete gross resection, and 21 of 74 had positive microscopic margin. The dose of HDR-IORT ranged from 10 to 18 Gy. RESULTS: With a median follow-up of 22 months, the 5-year local control, distant metastasis disease-free, disease-free, and overall survival rates were 39%, 39%, 23%, and 23%, respectively. The only predictor of improved local control was a negative margin of resection with a 5-year local control rate of 43%, compared to 26% in those with positive margin (p = 0.02). For overall survival, a negative microscopic margin (p = 0.04) and the use of IORT + EBRT (p = 0.04) were significant predictors of improved survival. The incidence of peripheral neuropathy was 16%. CONCLUSION: The results with HDR-IORT in this group of patients are encouraging. Further improvements in local and distant control are still needed.