Sacropelvic resection and intraoperative radiation therapy: feasibility, technical description and early clinical results

Sarcomas and locally recurrent colorectal carcinomas are disease entities in which sacral resection is an effective alternative for meaningful palliation with a limited cure expectation. To provide local control, pain palliation and a marginal expectation of definitive cure, a multimodality approach including external beam radiation therapy, surgical resection, and intraoperative radiation therapy (IORT), has been developed for patients with locally recurrent rectal cancers and primary sarcomas of the sacro-pelvic región. Seven consecutive patients (5 females; 2 males; ages, 40–75) underwent surgical exploration, sacrectomy, and IORT, between 1997 and 2000. IORT doses ranged from 10 to 12.5 Gy. External beam irradiation (EBRT) was used in six patients not previously irradiated (85%). Only 1 patient (14.2%) had received postoperative chemotherapy. Level of sacral resection: S2–S3 in 3 patients and S3–S4 in 2 patients. One patient with osteosarcoma underwent a posterior approach only, requiring removal of the posterior sacral table exclusively. An exclusively anterior approach was used in another patient with recurrent rectal cancer involving uterus, vagina and presacral fascia, requiring selective removal of the anterior sacral table. Margins: clear in 5 and microscopically involved in 2 patients. Postoperative mortality rate: 1 patient (14.2%). Three patients (42%) suffered major postoperative complications. Follow-up was available on six patients: time from surgery ranging from 1 to 36 (median 12.5) months. At the time of analysis, 5 out of 6 patients were alive without recurrent symptoms. Intensified local radiosurgical treatment with sacropelvic resection in conjunction with IORT provides palliation and offers potential for cure in patients with locally recurrent rectal cancer and sacropelvic sarcomas.     

Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.     

Intraoperative radiation therapy

The modern use of intraoperative radiation therapy (IORT) was initiated by the studies of Abe and colleagues at the University of Kyoto. This work stimulated significant laboratory and clinical investigation into the use of IORT throughout Japan, Europe, and the United States. Because of this experience, single high doses of irradiation can be safely delivered to a tumor volume in appropriate clinical situations. Most importantly, this high dose of additional radiation treatment yields improved local control of selected tumors. Treatment programs of external beam radiation therapy, surgical resection, and IORT for patients with locally advanced primary and recurrent rectal carcinoma and retroperitoneal sarcoma have yielded excellent local control and higher survival rates. The future of IORT will be in the successful integration of this therapy into multimodality treatment programs of chemotherapy, external beam irradiation, and surgery for locally advanced malignancies. Received: August 20, 2001     

Significance of intraoperative radiation therapy and high cumulative radiation doses in retroperitoneal soft tissue sarcoma

IntroductionIn retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates remain high despite more aggressive surgical approaches. Since wide resection margins cannot be achieved in all patients, application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear.Material and methodsPatients undergoing resection of primary or recurrent retroperitoneal STS at the University of Heidelberg Department of General, Visceral and Transplantation Surgery were retrospectively analyzed. Univariate Kaplan-Meyer and multivariate Cox regression analyses were performed to identify predictors of LR-free survival and to investigate the impact of IORT and high cumulative radiation doses. Analyses with propensity-score matched subgroups for IORT and cumulative radiation dose were performed to control for selection bias. Subgroup analyses for patients with retroperitoneal liposarcoma were likewise performed.Results272 patients were identified. Recurrent tumors, histology of dedifferentiated liposarcoma or unclassified sarcoma and microscopically incomplete resection were associated with decreased LR-free survival. In liposarcoma, only recurrent and dedifferentiated tumors were confirmed as poor prognostic factors concerning LR. IORT and cumulative radiation doses exceeding 60 Gy did not influence LR rates (estimated 5-year LR-free survival: IORT: 39%, non-IORT: 46%; p = 0.79).ConclusionIn this retrospective evaluation, additional application of IORT does not significantly influence oncological outcome in retroperitoneal soft tissue sarcoma. Randomized trials are needed to clarify the benefit of IORT.     

Dosimetry of leakage doses from a mobile accelerator for IORT and legal issues for its clinical use in Japan

Background. Despite the clinical usefulness of intraoperative radiotherapy, this treatment requires large staff numbers. A mobile linear accelerator unit dedicated for electron beam intraoperative radiation therapy (IORT) is now commercially available, but its use is not permitted by Japanese regulations on medical radiation. Methods. The mobile accelerator is now the subject of a clinical trial at the University of California, San Francisco (UCSF). Before the trial began, leakage doses around the facility were evaluated. Leakage doses around the accelerator were measured, and leakage doses arising from the operating room were monitored in the adjoining corridors, on the doors around the room and in the rooms on the floors above and below. Results. When the machine is used under the proper conditions, the leakage doses can be lower than the limit determined by the Japanese Radiation Safety Law. Conclusions. The mobile accelerator is a promising tool for IORT, and it is suggested that the Medical Treatment Law should be modified to permit the use of the machine in Japan. Received: May 28, 1998 / Accepted: February 1, 1999     

Use of ileal urinary diversion in conjunction with intraoperative radiotherapy

Intraoperative radiotherapy (IORT) was introduced in the 1970s as a new modality of cancer therapy. It has been especially useful after local irradiation or surgical failure. We report on the use of IORT in 13 patients with pelvic tumors requiring urinary diversion. All 13 were managed with ileal conduits. Despite the associated problems of prior abdominal procedures (11/13 patients), prior external beam radiation to the pelvis (11/13 patients), systemic chemotherapy (4/13 patients), and prolonged operative time (> 10 hours), perioperative mortality (1/13) and morbidity rates were low. We conclude that in cases of prior colonic resection and pelvic radiation, potentially irradiated ileum can be safely used for urinary diversion. © 1995 Wiley-Liss, Inc.     

Intraoperative radiotherapy during lung cancer surgery: technical description and early clinical results

A phase I-II study of intraoperative radiotherapy (IORT) for Stage III lung cancer was performed in 34 patients during a period of 58 months. Loco-regional treatment included tumor resection if technically feasible, IORT boost of electron beams using moderate single doses (10-15 Gy) to tumor bearing areas and external photon beam irradiation (46-50 Gy in 5 weeks) using conventional fields. Indications for this study were unresectable hiliar tumors (14, 41%), and mediastinal, hiliar and/or chest wall residual disease following resection (20, 59%). Thirty-four procedures, with 40 IORT fields, have been analyzed to describe the relevant technical aspects and the toxicity. IORT was delivered using acrylic transparent cones of different diameters. Surgical approach consisted in a lateral thoracotomy in all patients (21 right side and 13 left side). Tissues included within the IORT field were: tumor or residual tumor tissues (34, 100%), collapsed lung parenchyma and main bronchus not surgically manipulated (14, 41%), bronchial stump and vascular suture following resection (19, 55%), mediastinal structures (20, 58%), and brachial plexus (1, 3%). The bronchial suture was covered with pleural or pericardial flap after IORT in 10 cases (29%). Life threatening toxicity related to IORT consisted in broncho-pleural fistula (1, 3%) and massive hemoptysis (1, 3%). Other reversible toxic events were acute pneumonitis (12, 85%) and esophagitis (10, 50%). Long term asymptomatic lung fibrosis was detected in 11 cases (32%). Median survival time for the entire group has been 12 months. With a median follow-up time of 12 months the freedom from thoracic recurrence rate is 30% (65% in cases with tumor resection). Projected actuarial survival rates at 4 years were 28% for resected group and 7% for unresected cases. This experience supports IORT as a feasible alternative modality to be used in the management of locally advanced lung cancer. Tolerance of thoracic organs to moderate doses of IORT appeared to be adequate and local control is achieved in certain patients. These results deserve further investigation and confirmation trials.     

Long-term survival and patterns of failure after postoperative radiation therapy for subtotally resected rectal adenocarcinoma

Between 1977 and 1984, 17 patients received external beam irradiation after subtotal resection of rectal carcinoma. Ten patients had microscopic residual disease and 7 had gross residual disease. In the group with microscopic residual disease, 4 had tumor cut through with pathologically involved margins, 5 had adjacent unresected structures that were biopsy positive, and 1 had tumor spillage into the pelvis. The patients with gross residual disease were noted by the surgeon to have visible tumor after maximal debulking. Nine of 17 cases had involved pelvic lymph nodes. Radiation was administered to the pelvis with 4, 6, or 10 MV photons. Doses ranged from 40 to 60 Gy, with a median dose of 50 Gy given at 1.8 to 2.0 Gy per fraction, 5 days per week. Three patients received bacillus Calmette-Guérin (BCG), 2 received 5-fluorouracil (5-FU), and 1 received hycanthone. Thirteen of the 17 patients (76%) experienced local failure and, of these, 10 also developed distant disease. No patients developed distant metastasis in the absence of local failure. Local control was achieved in 3 of 10 patients (30%) with microscopic residual and 1 of 7 (14%) with gross residual. Four of the 17 patients (24%) have remained free of disease for greater than 5 years. External beam irradiation is capable of producing long-term survival and local control in a minority of patients with rectal cancer after subtotal resection. Investigation of more aggressive forms of therapy such as the addition of intraoperative irradiation, brachytherapy, radiation dose modifiers, and chemotherapy is warranted.     

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.     

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.     

Comparisons between the KKU-Model and Conventional Rectal Tubes as Markers for Checking Rectal Doses during Intracavitary Brachytherapy of Cervical Cancer

Background: To compare the KKU-model rectal tube (KKU-tube) and the conventional rectal tube (CRT) for checking rectal doses during high-dose-rate intracavitary brachytherapy (HDR-ICBT) of cervical cancer. Materials and Methods: Between February 2010 and January 2011, thirty -two patients with cervical cancer were enrolled and treated with external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT). The KKU-tube and CRT were applied intrarectally in the same patients at alternate sessions as references forcalculation of rectal doses during ICBT. The gold standard references of rectum anatomical markers which are most proximal to radiation sources were anterior rectal walls (ARW) adjacent to the uterine cervix demonstrated by barium sulfate suspension enema. The calculated rectal doses derived from actual anterior rectal walls, CRT and the anterior surfaces of the KKU-tubes were compared by using the paired t-test. The pain caused by insertion of each type of rectal tube was assessed by the visual analogue scale (VAS). Results: The mean dose of CRT was lower than the mean dose of ARW (Dmean0-Dmean1) by 80.55±47.33 cGy (p-value <0.05). The mean dose of the KKU-tube was lower than the mean dose of ARW (Dmean0-Dmean2) by 30.82±24.20 cGy (p-value <0.05). The mean dose difference [(Dmean0-Dmean1)-(Dmean0-Dmean2)] was 49.72±51.60 cGy, which was statistically significant between 42.32 cGy -57.13 cGy with the t-value of 13.24 (p-value <0.05). The maximum rectal dose by using CRT was higher than the KKU-tube as much as 75.26 cGy and statistically significant with the t-score of 7.55 (p-value <0.05). The mean doses at the anterior rectal wall while using the CRTs and the KKU-tubes were not significantly different (p-value=0.09). The mean pain score during insertion of the CRT was significantly higher than the KKU-tube by a t-score of 6.15 (p-value <0.05) Conclusions: The KKU-model rectal tube was found to be an easily producible, applicable and reliable instrument as a reference for evaluating the rectal dose during ICBT of cervical cancer without negative effects on the patients.     

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.     

Are doses to ICRU reference points valuable for predicting late rectal and bladder morbidity after definitive radiotherapy in uterine cervix cancer?

AIMS AND BACKGROUND: To evaluate whether doses or dose rates at International Commission on Radiation Units (ICRU) reference points are of value for predicting risks of late rectal and bladder morbidity in patients with uterine cervical cancer who have undergone external beam radiotherapy and intracavitary irradiation. METHODS: Late rectal complications and late bladder complications were evaluated in 54 patients who were treated by external beam radiotherapy followed by intracavitary irradiation between January 1996 and December 1999. External beam radiotherapy was delivered in 1.8 Gy daily fractions to a whole pelvis dose of 50.4 Gy followed by intracavitary irradiation at total point A doses ranging from 75 Gy to 85 Gy. Intracavitary irradiation was performed with dose rates of 0.5-0.7 Gy/h to point A in most patients, but 8 patients were treated at a higher dose rate (0.83-1.15 Gy/h) to shorten the hospitalization period. Biologically effective doses for the reference points were calculated using a linear quadratic model. RESULTS: Grade 3 rectal and bladder morbidity by Radiation Therapy Oncology Group (RTOG) criteria developed in 4 patients (7.4%) and 1 (1.9%), respectively. An age of >60 years (P = 0.01) and a total dose to the rectal reference point of > or =80 Gy (P = 0.03) were found to be correlated with a higher rate of rectal morbidity. Total dose (> or =80 Gy), dose rate (> or = 0.75 Gy/h), and biologically effective doses (> or =135 Gy3) at the bladder reference point were found to be significant factors for the development of late bladder morbidity. By multivariate analysis, age was identified as the only significant factor of late rectal complications, and biologically effective doses at the bladder reference point was the only significant factor of late bladder complications. CONCLUSIONS: RTOG grade 3 late rectal and bladder morbidity developed in respectively 7.4% and 1.9% of the patients. The significant risk factors for late rectal and bladder morbidity were old age and biologically effective doses at the bladder reference point, respectively.     

A phase I/II study of intraoperative radiotherapy in advanced unresectable or recurrent carcinoma of the rectum: A radiation therapy oncology group (RTOG) study

The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.0001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recurrent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress. © 1993 Wiley-Liss, Inc.     

Efficacy and safety of intraoperative radiotherapy in rectal cancer: A systematic review and meta-analysis

BACKGROUNDIn recent years, intraoperative radiotherapy (IORT) has been increasingly used for the treatment of rectal cancer. However, the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.AIMTo evaluate the value of IORT for patients with rectal cancer.METHODSWe searched PubMed, Embase, Cochrane Library, Web of Science databases, and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer. Dichotomous variables were evaluated by odds ratio (OR) and 95% confidence interval (CI), hazard ratio (HR) and 95%CI was used as a summary statistic of survival outcomes. Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.RESULTSIn this study, 3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients, who are mainly residents of Europe, the United States, and Asia. Our results did not show significant differences in 5-year overall survival (HR = 0.80, 95%CI = 0.60-1.06; P = 0.126); 5-year disease-free survival (HR = 0.94, 95%CI = 0.73-1.22; P = 0.650); abscess (OR = 1.10, 95%CI = 0.67-1.80; P = 0.713), fistulae (OR = 0.79, 95%CI = 0.33-1.89; P = 0.600); wound complication (OR = 1.21, 95%CI = 0.62-2.36; P = 0.575); anastomotic leakage (OR = 1.09, 95%CI = 0.59-2.02; P = 0.775); and neurogenic bladder dysfunction (OR = 0.69, 95%CI = 0.31-1.55; P = 0.369). However, the meta-analysis of 5-year local control was significantly different (OR = 3.07, 95%CI = 1.66-5.66; P = 0.000).CONCLUSIONThe advantage of IORT is mainly reflected in 5-year local control, but it is not statistically significant for 5-year overall survival, 5-year disease-free survival, and complications.     

A new approach to adjuvant radiotherapy in rectal cancer

A sandwich technique of adjuvant radiotherapy was used to treat twenty-three patients with rectal cancer. In this technique, low dose preoperative irradiation (500 rad in one treatment) was given to all patients followed by immediate surgery (usually an A-P resection); on the basis of histopathological findings, patients with stage B₂ and C rectal cancer were selectively given 4500 rad post-operative irradiation in 5 weeks. Nine patients had early lesions (stage A and B₁) and did not receive postoperative irradiation. Thirteen patients had stage B₂ and C disease and hence received the full course of postoperative irradiation. One patient was found to have liver metastasis at the time of surgery, and hence received only palliative therapy. Follow-up of these twenty-three patients ranges from 10 months to 24 months with a median follow-up of 15 months. Treatment was well-tolerated with few side effects. Only two of the twenty-two patients who were treated for cure have failed to date. Both patients had stage C₂ disease; once patient developed an anterior abdominal wall recurrence in the surgical scar 3 months post-treatment and the second patient developed brain and bone metastases. No patients have failed in the pelvis. We feel this technique of adjuvant therapy is a logical approach to the treatment of rectal cancer and has potential for improving survival. The rationale for this approach to adjuvant radiotherapy is discussed together with implications for survival.     

Exclusion of small bowel from pelvis for postoperative radiotherapy for rectal cancer

The pelvis is the preferential site of disease when recurrence occurs after curative resection of rectal cancer. Postoperative adjuvant radiotherapy decreases local recurrence rates for Dukes stages B and C; however, after abdominoperineal or anterior resections, the small bowel descends into the lower pelvis, and, due to its low tolerance to radiation, optimal doses cannot be safely delivered unless the small bowel can be excluded from the pelvis. This can be achieved by cystopexy and/or by creating a pelvic sling with a knitted polypropylene mesh. Three cases are presented in which radiotherapy was satisfactorily delivered with these techniques.     

Preoperative irradiation for tethered rectal carcinoma

Twenty-eight patients with resectable but tethered rectal carcinomas were treated with preoperative irradiation (EBRT) and surgical resection. The 5-year actuarial disease-free survival and local control rates of these 28 patients were 66 and 76%, respectively. Two patients have developed local failure only, 2 patients concurrent local failures and distant metastases, and 4 patients distant metastases only. All local failures occurred in areas of tumor adherence to unresectable structures (sacrum, pelvic side wall). Patients with tethered rectal tumors are at risk for local failure despite preoperative irradiation and surgical resection. To improve local control in this subset of patients, an intraoperative radiation therapy (IORT) boost is given to areas of tumor adherence at resection following EBRT.     

Bone necrosis and tumor induction following experimental intraoperative irradiation

The bone of the lumbar vertebrae of 153 dogs was examined 2 and 5 years after intraoperative irradiation (IORT), fractionated external beam irradiation (EBRT), or the combination. Groups of dogs received 15 to 55 Gy IORT only, 10 to 47.5 Gy IORT combined with 50 Gy EBRT in 2 Gy fractions or 60 to 80 Gy EBRT in 30 fractions. Six MeV electrons were used for IORT, and EBRT was done using photons from a 6 MV linear accelerator. The paraaortic region was irradiated and the ventral part of the lumbar vertebrae was in the 90% isodose level. Two years after irradiation, the dose causing significant bone necrosis as determined by at least 50% empty lacunae in the vertebral cortex was 38.2 Gy IORT alone and 32.5 Gy IORT combined with EBRT. Five years after irradiation, the dose causing 50% empty lacunae was 28.5 Gy IORT only and 14.4 Gy IORT combined with EBRT. The ED50 for lesions of the ventral vertebral artery was 21.7 Gy IORT only and 20.1 Gy IORT combined with 50 Gy EBRT 2 years after irradiation and 27.0 Gy IORT only and 20.0 Gy IORT combined with 50 Gy EBRT 5 years after irradiation. All lesions after EBRT only were mild. Eight dogs developed osteosarcomas 4 to 5 years after irradiation, one at 47.5 Gy IORT only and the remainder at 25.0 Gy IORT and above combined with 50 Gy EBRT. In conclusion, the extent of empty lacunae, indicating bone necrosis, was more severe 5 years after irradiation than after 2 years. The effect of 50 Gy EBRT in 2 Gy fractions was equivalent to about 6 Gy IORT 2 years after irradiation and to about 14 Gy 5 years after irradiation. Based on these estimates, IORT doses of 10 to 15 Gy have an effect 5 times or greater than the amount given in 2 Gy fractions. Osteosarcomas occurred in 21% of dogs which received doses greater than 25 Gy IORT. Doses of 15 to 20 Gy IORT in combination with 50 Gy EBRT in 2 Gy fractions may be near the tolerance level for late developing bone injury.