The Role of Intraoperative Radiotherapy in Solid Tumors - Springer Link

Ann Surg Oncol (2009) 16:735–744 DOI 10.1245/s10434-008-0287-2

ORIGINAL ARTICLE – RADIATION ONCOLOGY

The Role of Intraoperative Radiotherapy in Solid Tumors A. R. Skandarajah, MBBS, MD, FRACS1, A. C. Lynch, MMed Sci, FRACS1, J. R. Mackay, FRCS, FRACS1, S. Ngan, FRCSEd, FRANZCR2, and A. G. Heriot, MD, FRCS, FRACS1 Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne 3002, Australia; 2Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne 3002, Australia 1

ABSTRACT Background. Combined multimodality therapy is becoming standard treatment for many solid tumors, but the role of intraoperative radiotherapy in the management of solid tumors remains uncertain. The aim is to review the indication, application, and outcomes of intraoperative radiotherapy in the management of nongynecological solid tumors. Methods. A literature search was performed using Medline, Embase, Ovid, and Cochrane database for studies between 1965 and 2008 assessing intraoperative radiotherapy, using the keywords ‘‘intraoperative radiotherapy,’’ ‘‘colorectal cancer,’’ ‘‘breast cancer,’’ ‘‘gastric cancer,’’ ‘‘pancreatic cancer,’’ ‘‘soft tissue tumor,’’ and ‘‘surgery.’’ Only publications in English with available abstracts and regarding adult humans were included, and the evidence was critically evaluated. Results. Our search retrieved 864 publications. After exclusion of nonclinical papers, duplicated papers and exclusion of brachytherapy papers, 77 papers were suitable to assess the current role of intraoperative radiotherapy. The clinical application and evidence base of intraoperative radiotherapy for each cancer is presented. Conclusions. Current studies in all common cancers show an additional benefit in local recurrence rates when intraoperative radiotherapy is included in the multimodal treatment. However, intraoperative radiotherapy may not improve overall survival and has significant morbidity depending on the site of the tumor. Intraoperative radiotherapy does have a role in the multidisciplinary management of solid tumors, but further studies are required to more precisely determine the extent of benefit. Ó Society of Surgical Oncology 2009 First Received: 12 August 2008; Published Online: 14 January 2009 A. R. Skandarajah, MBBS, MD, FRACS e-mail: [email protected]

The application of intraoperative radiotherapy (IORT) for prevention and treatment of local recurrence of solid tumors has evolved over the last 3 decades. It was first described in 1906 by Comas and Prio.1 The modern use of IORT developed in the 1960s, with construction of dedicated IORT facilities over the last 2 decades, has obviated the requirement for transport between radiotherapy and theater. However, the cost of refitting or building a shielded operating theater, complete with linear accelerator and dedicated only to operative cases, is significant. There is increasing emphasis on multidisciplinary management of solid tumors to improve outcome. Radiotherapy has been demonstrated to both reduce local recurrence and to facilitate less radical surgery without deterioration in outcome. The aim of IORT is to improve local control and disease-free survival after surgical resection, particularly in the situation of close or positive margins, because of either concern over cosmesis or anatomical limitations. Direct visualization and placement of the applicator to the tumor bed and intraoperative protection of vulnerable structures enables an increased targeted dose of radiation because of displacement of the usual dose-limiting tissues.2 This review aims to explore current evidence and rationale for the use of IORT in solid tumors in nongynecological solid tumors. METHODS A literature search was performed using Medline, Embase, Ovid, and Cochrane database for studies between 1965 and 2008, assessing the use and guidelines regarding intraoperative radiotherapy in the multimodal management of solid tumors in nongynecological surgery. The following text searches and search headings and their combinations were used: ‘‘intraoperative radiotherapy,’’ ‘‘colorectal cancer,’’ ‘‘breast cancer,’’ ‘‘gastric cancer,’’ ‘‘pancreatic cancer,’’ ‘‘sarcoma,’’ and ‘‘surgery.’’ The ‘‘related articles’’

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A. R. Skandarajah et al.

function was used to broaden the search, and all abstracts, studies, and citations scanned were reviewed. The search was restricted to English language articles and human studies. The references from articles were also used. The scientific quality of the individual papers included in the tables were assessed using the Scottish Intercollegiate Guidelines Network grading recommendations.3,4 All the papers included were case series with a level of evidence of 3. The papers assessed for this review were in the low range of the scientific-validity scale, which should be considered when assessing the stated conclusions. This systematic review is however a critical assessment of the published evidence available. RESULTS

FIG. 1 Applicator placed in pelvis postpelvic exenteration

Our research retrieved 864 publications. After exclusion of nonclinical papers, duplicated papers, and brachytherapy papers, 77 papers were suitable to assess the current role of intraoperative radiotherapy. The clinical application and evidence base of intraoperative radiotherapy for each cancer is presented. IOERT and HDR-IORT IORT is given as a single fraction of 10 to 20 Gray (Gy). While single fractions are considered radiobiologically inferior to conventional fractionated radiotherapy, due to impaired cellular repair of surrounding tissue,5 protection of these tissues allows focused radiation, which is biologically equivalent to two to three times that of conventional fractionation.6,7 IORT can either be delivered by electron beams produced by linear accelerators (IOERT) or high dose rate brachytherapy (HDR-IORT).7 Most clinical experiences are based on IOERT. It requires a dedicated operating room with a linear accelerator and appropriate radiation protection facilities, a radiation therapy control console adjacent to the theater, and remote patient monitoring facilities. Mobile IOERT units have been developed involving a C-arm linear accelerator design and generally have a quicker dose-delivery.8 HDR-IORT on the other hand involves an applicator made of soft plastic material with embedded hollow catheters placed on the site to be irradiated. HDR-IORT has the advantage of flexible applicators that can be molded to access all areas, especially in the pelvis (Fig. 1). The applicator is then connected to a HDR afterloader, via guidetubes, which contains an iridium-192 source. (Fig. 2).Traditional low dose rate (LDR) brachytherapy involves placement of hollow catheters in the area that requires irradiation at the time of surgery, but the

FIG. 2 Applicator attached to high-dose gamma-emitting source

radioactive source is manually loaded after the operation. LDR has much longer delivery time (typical delivery time for 10 Gy with LDR is 10 hours and HDR is 10 minutes). Prior to treatment delivery, the dosimetry parameters are calculated by the radiation oncologist, radiation therapist, and physicist. Once the setup is completed and secure, all staff must leave the operating theater before radiation can be commenced, with the patient being monitored remotely. Typically, the IORT-HDR procedure will add a total of 45 minutes to the overall operating time. IOERT has the advantage that the depth of penetration of the electron beam can be varied by varying the energy of the electron beam. It can deliver radiation up to 5.5 cm. HDR-IORT provides more flexibility in terms of customizing the HDR applicator to fit the shape and size of the irradiated area. It can be used for narrow areas deep in the pelvis such as the back of the prostate gland, which is usually not accessible by the much larger IOERT machine. However, the effective depth of a single-plane HDT-IORT

Intraoperative Radiotherapy: A Review

737

is about 1 cm (since there is rapid dose fall off away from the radioactive sources), and therefore prior maximal debulking of the tumor is necessary. (Figs. 3 and 4.) Clinical Applications Current evaluation of IORT is limited by the paucity of randomized controlled trials and the large number of patients required to power such studies. Most studies are single-institution series with retrospective control comparisons. However, there are a number of prospective randomized studies under way. Colorectal Cancer The two major applications of IORT in colorectal cancer are in locally advanced or recurrent cancer where the possibility of having an R1 (microscopically involved) margin is likely. Locally Advanced Colorectal Cancer At Massachusetts General Hospital, 145 patients with locally advanced rectal cancer were treated with preoperative radiotherapy, and the majority of these received concurrent chemotherapy.9 Of these, 73 patients had tumor adherence or residual disease and were treated with 10 Gy of IORT. Those patients who had complete pathological clearance or R0 resection had local control of 89% and disease-free survival in 69% at 5 years. The local control and disease-free survival at 5 years for those with an R1 margin was 68% and 40%, respectively, and 57% and 14%, respectively, in those with an R2 (macroscopically involved) margin. These figures were favorable compared with historic controls. A similarly large institutional study by Taylor et al. from the Mayo Clinic examined the role of IORT in locally advanced (25) and recurrent colonic tumors (73) with a 49% and 24.9% 5-year disease-free survival rate.10 In the

FIG. 3 IOERT isodose with 12 MeV

FIG. 4 HDR-IORT isodose with iridium-192 source

locally advanced group, only 3 patients died due to local failure (12%) (Table 1). Ferenschild et al. examined the role of IORT in 27 patients with locally advanced rectal cancer who had received preoperative chemoradiotherapy and had a circumferential resection margin of \2 mm determined by frozen section.11 HDR-IORT was administered in dosage of 10 Gr. Eight patients with an R1 or R2 margin were excluded from IORT due to prior irradiation, comorbidities, or lack of availability of IORT. The local control and disease-free survival rates for the patients receiving IORT was 58% and 38%, respectively. All 8 patients who were excluded from IORT developed a local recurrence and died within 5 years. There are several small studies with similar findings; the patterns of disease-free survival were determined by the completeness of surgical resection.12–17 Recurrent Rectal Cancer Resection margin involvement has been demonstrated to be the most important prognostic factor in patients undergoing surgery for

738 TABLE 1 Major series of IORT use in locally advanced or recurrent colorectal cancer


Series

Year

No. of patients receiving IORT

1991

101

Margins

Local control (%)

Disease-free survival 5 years (%)

Locally advanced Massachuusetts13,15 Mayo

18

56

Spain66

2002

100

Netherlands11

2006

27

Cleveland IORT was given as part of multimodality treatment of rectal cancer

1997

67

b

2 years follow-up, mobile electron beam device

89

63

68

40

R0/1

95

59

R2

75

21

95 R0

72

66

R1

58

38

100

50

47 21

21 7

2008

16

Massachusetts68,69

2006

41

R0/1 R2

Mayo70

1995

106

R0/1 60

9

Mayo10,20

2001

175

60

12–20a

Cleveland67

2008

18

95

67b

Locally recurrent

a

12% in group who had received previous external beam, 20% in nonirradiated patients

R0 R1

R2

recurrent rectal cancer. The ability to obtain an R0 resection (clear margins) at surgery is complicated by the disruption of surgical planes by prior surgery, and frequently, extended resections including enbloc cystoprostatectomy or vaginectomy/hysterectomy for anterior extension or sacrectomy for posterior extension are required. Overall 5-year survival of up to 40% in all patients has been demonstrated by major centers, but lateral recurrence remains a major problem.18 Bony limits to resection such as the pelvic sidewall increase the risk of involved margins, which has led to a number of centers using IORT to improve outcome. A study by Mannaerts et al. compared 19 patients undergoing preoperative radiotherapy and surgery with 33 patients who received multimodality treatment including IORT.19 Survival was improved in the IORT group (11% vs. 60%). However, the R0 resection rate was also significantly greater in the IORT group (7 of 19 vs. 21 of 31), and hence it is difficult to prove the benefit of IORT as the groups are not directly comparable. A number of studies using multimodality treatment for recurrent rectal cancer comprising preoperative external beam radiotherapy, surgery, and IORT have shown an improvement in local control in patients receiving IORT,5,19–22 although this has not been a universal finding.23,24 The most extensive experience of IORT for recurrent rectal cancer has been reported by the Mayo Clinic.25 Of 304 patients undergoing resection, 131 received IORT, 52% with palliative intent and 33% with curative intent, with 5-year survivals of 21% and 27%, respectively. They concluded that ‘‘the possibility of selection bias precludes the ability to draw definitive conclusions about the independent contribution of the IORT

33

treatment,’’ but felt that as IORT has demonstrated good local control rates and overall results with multimodality treatment were good, combined therapy should continue to be applied selectively. Although IORT aims to minimize local tissue toxicity by targeting therapy, its inclusion in the multimodal treatment of colorectal cancer is not without morbidity, especially as there is already significant morbidity associated with surgery for advanced and recurrent rectal cancers. In the Mayo series, 20% had severe treatmentrelated complications including enterocutaneous fistula, duodenal obstruction, debilitating neuropathy, and short bowel syndrome requiring total parenteral nutrition.10 Similarly, Martinez-Monge found complications of Grade 4–5 radiation toxicity in 19% of patients.7 While IORT is not solely responsible for the complication rate, the pelvic nerves are particularly vulnerable,26 and doses greater than 15 Gy appear to be the threshold for clinical neuropathy.18 Ureteric stenosis occurs in between 0 and 7% of cases, but can often be managed with ureteric stents.27–29 Sacral osteonecrosis is rare, but is probably related to overdose at areas of overlapping radiation fields.30 Breast Cancer The standard treatment for early breast cancer is breast-conserving surgery and whole-breast external beam radiation.31,32 There is no difference in overall survival with this regime compared with total mastectomy.31 Despite this, many women still proceed to mastectomy; lack of access to radiotherapy centers and the long course of treatment are deterrents to radiotherapy. Studies of IORT in early breast cancer are evaluating IORT


as an adjuvant to standard treatment or as replacement to whole-breast radiotherapy (WBRT). Most local recurrences in breast cancer occur in the tissues immediately adjacent to the tumor and often within the first 5 years post-treatment.33,34 Adjuvant IORT has the advantages of targeting treatment to the high-risk breast and minimizing the cosmetic effects of WBRT by protection of skin and shielding of the chest wall as appropriate.35 As the sole form of adjuvant radiotherapy, it has the theoretical advantages of being completed at one sitting without further delaying adjuvant hormonal or chemotherapy. Potentially, once IORT facilities are established, the cost of radiotherapy for early breast cancer may be significantly reduced.34 There are a number of forms of accelerated partialbreast radiotherapy. The Intrabeam, as used in the TARGIT trial, delivers rapidly attenuated radiation doses enabling the tissue immediately at the surgical margin to receive higher doses than distal tissues.36 The dose delivered is usually 20 Gy, and the spherical applicators sit in the cavity following wide local excision. Breast IORT has some inherent albeit anticipated disadvantages. Local recurrence is strongly associated with positive margins.33 Standard practice in breast-conserving surgery is to reexcise positive margins before WBRT. The lack of pretreatment pathology, including knowledge of margins and predictors of local recurrence such as ductal carcinoma in situ and extensive intraductal component, imply that IORT may be given inappropriately in circumstances where WBRT is indicated. Intraoperative frozen sections may be used to reduce positive margins. Alternatively, a staged IORT process as a second procedure may be preferable, once the pathology is known. There are several randomized trials evaluating IORT in breast cancer. Ciccone et al. randomized patients to electron beam IORT (79) versus WBRT (69) in patients with T1 or T2 breast cancers.37 At 3 years, there were no differences between the groups in terms of local recurrence, cosmesis, or local toxicity. The results of other randomized trials are still pending. Veronesi et al. have randomized patients with T1 or T2 tumors to 21 Gy of IORT or WBRT.38 The IORT device uses low-energy X-rays (generally considered inferior to electron beam).34 Two trials currently accruing are the TARGIT and NSABP B-39 trials. TARGIT compares IORT versus WBRT using the Intrabeam. To date, 16 international institutions have accrued 779 patients. Patients are randomized to IORT immediately or postoperative IORT at a second sitting. The inclusion criteria are early breast cancers (T1-3, N0) with exclusion of multifocal or multicentric cancer, bilateral cancers, tumors with extensive intraductal component (EIC), invasive lobular cancer, or node-positive cancers, all factors that increase the risk of local recurrence.36

739

NSABP-B-39 is a randomized control trial comparing IORT with WBRT in T1–2 tumors, but including DCIS and node-positive patients with \3 nodes. A subgroup analysis will compare the different types of radiation techniques— multicatheter brachytherapy, Mammosite balloons catheter against 3D conformal external beam radiation.39 Stitzenberg et al.40,41 evaluated the technique of in situ IORT whereby IORT is administered prior to tumor removal. The rationale was that lower doses and smaller target volumes could be achieved by treating an undisturbed tumor bed with the potential of better cosmesis, particularly if the pathology then necessitates adjuvant WBRT. In the short-term follow-up of 3 years, two patients had acute toxicity of mastitis and delayed wound healing. A number of case series have also been published. These are summarized in Table 2. As in colorectal cancer, the use of IORT has also been proposed in localized breast recurrences after previous external beam. With a median follow-up of only 26 months, Kraus-Tiefenbacher had no local recurrences in 15 patients and no Grade 3/4 toxicities.42 Three patients had distal metastases of which one died at 26 months. Potentially, IORT could be used for local control rather than offering a mastectomy, which is currently standard management.42 Despite promising early results, the data supporting IORT is immature, and outside the setting of a clinical trial, use of IORT in early breast cancer or in local recurrence is as yet not recommended.35,43 Gastric Cancer A decrease in locoregional recurrence with use of radiotherapy in gastric cancer has been demonstrated in trials such as Macdonald’s adjuvant chemoradiotherapy trial.44 However, the benefit is achieved at the price of potential toxicity to other organs such as the liver and kidney and to the anastomosis. Abe et al. have pioneered the modern use of IORT in gastric cancer as single or multimodality treatments for gastric cancer.45,46 The first large-scale study followed 38 patients postresection or attempted resection treated with 25 to 40 Gy in 1974. This was a dose-calculation study, but also concluded that IORT was not indicated unless the primary tumor could be removed. However, in a follow-up study in 1981, when compared with historic surgery-alone controls, there was a stage-for-stage benefit for IORT.45 Abe refined the data in a randomized control trial that same year, with 110 patients in the control group, and 84 patients were treated with addition 30 to 35 Gy of IORT. At 5 years, the overall survival was 88% versus 93% for Stage I, 77% versus 54 for Stage II, 44% versus 36% for Stage III and 19% versus 0% for Stage IV, attributing IORT to decreased locoregional recurrence and hence increased overall survival.45 While an update in 1988 reiterated the benefits of

740


TABLE 2 Major published series of IORT use in early or recurrent breast cancer Center MCO/CRLC71,72 Salzburg

73

Milano74

Year

Stage of breast cancer

Number

Local control

Disease-free survival

1997

EBC

72

99%

100% (2 years)

2002

EBC

170

165/165

2001

EBC

115 to IORT

100%

99% (2 years) 100% (2 years)

115 no IORT MCO Medical College of Ohio CRLC Centre Regional de Lutte Contre le Cancer

IORT for Stage II–IV,47 this was further studied according to histological features. A 10% survival benefit for tumors with serosal invasion, N2 or N3 disease was demonstrated but not in those patients with Stage I or N1 disease.48,49 Two other randomized trials have been published evaluating IORT versus EBRT for gastric cancer. The NCI randomized patients to 29 Gy of IORT (16) or 5 weeks of 50 Gy postoperatively (25). The majority (88%) of patients were Stage III or IV. This study showed no significant difference between groups in effect on locoregional recurrence and survival.50 Similarly, Skoropad et al. in 2000 published a trial to compare preoperative, radiotherapy, IORT, and surgery alone. The radiation-treated group had a 50% postoperative complication rate with no overall survival benefit.51 The paucity of trials over the last decade perhaps highlights the minimal efficacy of IORT in gastric cancer. In 2006, another retrospective study evaluated IORT against historic controls, demonstrating a survival difference of 5% in Stage II–IV disease for those receiving a D2 but not a D3 resection.52 Most recently, Drognitz et al. published a retrospective nonrandomized study of a subset of 61 patients with an R0 resection who received IORT.53 For each stage, there was no difference in overall survival and a significant increased complication rate in the IORT group (44.3% with IORT vs. 19.7%; P \ .05). Its use may be best in consideration of local salvage therapy for recurrence as part of multimodal therapy.54 Trials evaluating IORT use in gastric cancer are summarized in Table 3. Pancreatic Cancer Although only 20% of pancreatic cancers tumors are resectable, by pancreaticoduodenostomy, a Whipple procedure may not ensure an R0 resection. Adjuvant chemoradiation has been proven to prolong median survival, but routine use of IORT is not established. As the resectability rate is 20%, studies are very small and conclusions drawn are not statistically significant. In a retrospective study, Zerbi et al.55 compared local recurrence, tolerance, and overall survival in groups with or without IORT using a linear accelerator (electron beam). The groups were well matched for age, sex, stage,

and size. Despite a decrease in local recurrence in those receiving IORT (27%) versus without IORT (56.3) (P \ .01), there was no statistically significant difference in disease-free survival and overall survival. Perioperative complications were not related to the use of IORT. The only randomized study conducted by the National Cancer Institute evaluated the use of 20 Gy or IORT in 12 patients and 12 controls. Once again, the use of IORT decreased local recurrence (33%) compared with 100% of the control population, but had no impact on overall survival.56 Other studies evaluating IORT in pancreatic cancer have failed to show an overall benefit of IORT to multimodal treatment of pancreatic cancer.57 Soft Tissue Tumors Soft tissue sarcoma has a high risk of local recurrence, and extensive surgery combined with external beam radiotherapy is frequently used to improve local control. The value of IORT in the multimodal treatment of retroperitoneal sarcoma is of paramount importance due to their frequent proximity to radiation dose limiting organs. IORT has the advantage of being applied with protection of surrounding structures, but is clearly not without complication. In a pilot study, Bussieres et al. used a dose of 17 Gy for 19 patients with retroperitoneal sarcoma (14 primary and 5 recurrent). Thirteen patients had additional external beam radiotherapy, and nine had adjuvant chemotherapy. Despite a 60% disease-free survival rate, 53% suffered immediate or delayed radiotherapy-related complications including a lethal iliac artery discruption.58 Of the comparative studies, only the randomized study by Sindelar et al. compared IORT and postoperative EBT versus EBT alone. They demonstrated a local recurrence rate in 40 versus 80%, respectively, but showed no overall survival difference at 5 years. Those receiving IORT had fewer radiation enteritis events, but more disabling peripheral neuropathies.59–61 Lehnert et al. examined the use of IORT in 92 (of 251) patients with soft tissue tumors, both primary and recurrent of the extremities, the trunk, or the retroperitoneum. Compared to their non-IORT patients, surgical complications, especially infectious complications were more frequent in the IORT group (P = .03). However,

Intraoperative Radiotherapy: A Review TABLE 3 Major published series of IORT use in gastric cancer

741

Series

Year

No. of patients

Stage

Disease-free survival

110 with IORT

Stage I

88 vs. 93%

84 no IORT

Stage II

77 vs. 54%

Stage III

44 vs. 36%

Stage IV

19 vs. 0%

Prospective randomized trials Abe45

Abe

48

1981

1995

94 IORT 127 no IORT

NCI50

1993

Stage I

96 vs. 100% (NS)

Stage II

66 vs. 78%

Stage III

51 vs. 60%*

Stage IV

14 vs. 33% 56%a

16 with IORT

25 with EBRT Russian51 Case series Abe75

2000

1980

8% 40 with IORT

53%a

38 preop EBRT

50%

38 vs. historic controls

Stage I

100 vs. 80% (no IORT)

Stage II

40 vs. 55%

Stage III Coquard76

1997

Martinez-Monge77 2000 10% better disease free-survival in those with serosal invasion after IORT

20 vs. 16%

63

25%b

27 IORT and EBRT

11.1 vs. 20% NS

35 EBRT only Qin52

2006

106 vs. 441 historic controls Stage I

100 vs. 93% NS

Stage II

100 vs. 81

NS not significant

Stage II

60 vs. 45

a

Stage IV

14 vs. 10%

Stage I/II

76 vs. 18% NS

No difference in overall survival

Drognitz53

2008

b

Lymphadenectomy limited in 90%

in multivariate analysis, the use of IORT reduced local recurrence by 40% (P = .03).62 The benefit in local recurrence needs to be carefully considered against the complications arising from addition of IORT.63 Definitive intraoperative high-dose radiotherapy for localized osteosarcoma in the extremities is effective in tumor control. However, fracture of the underlying irradiated bone can be significant.64 Prophylactic intramedullary nailing in selected patients may be appropriate.65 CONCLUSIONS Current studies in all common cancers show an additional benefit in local recurrence rates when IORT is included in the multimodal treatment. While IORT may decrease local recurrence in rectal cancers, particularly those with R1 resection margins, studies are underpowered and an R0 surgical margin is the most important factor to predict local recurrence. In breast cancer, a number of randomized trials are pending with regard to IORT versus whole-breast irradiation for early breast cancer. However these trials do not address a comparison with partial-breast

61 vs. 61 historic controls

Stage III/IV 21 vs. 14% NS

irradiation or the role of no radiation in early breast cancers with favorable pathological features in a postmenopausal patient. IORT in gastric cancer has been extensively studied with a minor benefit in decreasing local recurrence but with significant morbidity. Based on the most recent result of randomized trials showing no difference in local recurrence or overall survival, IORT is unlikely to be embraced in the multimodal treatment of gastric cancer or pancreatic cancer. Encouraging decreases in local recurrence have been demonstrated in soft tissue tumors but with no difference in overall and again with disabling morbidity. The role of IORT in nongynecological solid tumors is yet to be clearly established. The benefits of decreasing local recurrence in locally advanced and recurrent tumors must be weighed up against the morbidity of radiation complications. Its role in early breast cancer may decrease the cost and need of access to radiotherapy resources, but must be evaluated against partial-breast irradiation strategies. The utility in difficult recurrent colorectal tumors or locally advanced tumors is promising, but the decision to include IORT in the multimodal treatment of solid tumors must be individualized. IORT does have a role in the

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