Medical Policy

 

Subject: External Beam Intraoperative Radiation Therapy
Document #: THER-RAD.00004 Publish Date:    12/27/2017
Status: Revised Last Review Date:    05/04/2017

Description/Scope

This document addresses the delivery of external beam radiation therapy during surgery. External beam intraoperative radiation therapy (IORT), performed with either electron beams (IOERT) or photon beams, is a technique involving radiation treatment (radiotherapy) delivered to the tumor bed, regional lymph nodes, or both during a surgical procedure. IORT delivers a "boost" of radiation to these areas while sparing the surrounding normal tissue and organs. IORT delivered as partial breast irradiation (PBI) treats the breast with a single dose of radiation delivered to the exposed tumor bed during breast-conserving surgery. PBI is an alternative to whole breast irradiation (WBI) in the treatment of breast cancer.

Note: The delivery of intraoperative brachytherapy as a form of radiation therapy is addressed separately in the following document:

Note: Please see the following documents for information concerning other forms of radiation therapy:

Position Statement

Medically Necessary:

  1. External beam intraoperative radiation therapy is considered medically necessary as the sole source of additional radiotherapy at the time of surgical excision for colorectal cancer, pancreatic cancer, pelvic cancers (for example, cervical or uterine), soft tissue sarcomas, or breast cancer when the following criteria are met:
    1. Tumor cannot be completely removed; or
    2. Tumor has a high risk of recurring in surrounding tissues; and
    3. Intraoperative radiation therapy augments conventional external beam radiation therapy.
  2. External beam intraoperative partial breast irradiation (electron or low-energy x-ray radiotherapy) is considered medically necessary as an alternative to whole breast irradiation in the treatment of early stage breast cancer when all of the following criteria are met:
    1. Individual is 50 years of age or older; and
    2. Clinically node negative on either preoperative physical examination (that is, non-palpable node[s]), or medical imaging if performed (for example, mammography, magnetic resonance imaging [MRI], or ultrasound); and
    3. Tumor is either :
      1. Invasive ductal carcinoma measuring less than or equal to 2 centimeters (T1 disease) with negative margin widths of greater than or equal to 2 millimeters, no lymphovascular space invasion, estrogen-receptor positive (ER+), and BRCA negative; or
      2. Low or intermediate nuclear grade, screen-detected ductal carcinoma in situ measuring less than or equal to 2.5 centimeters with negative margin widths of greater than or equal to 3 millimeters.

Investigational and Not Medically Necessary:

  1. External beam intraoperative radiation therapy is considered investigational and not medically necessary when the above criteria are not met, and for all other indications.
  2. External beam intraoperative partial breast irradiation is considered investigational and not medically necessary for the treatment of breast cancer when the above criteria are not met.
Rationale

External beam intraoperative radiation therapy (IORT), delivered with either electron beams (IOERT) or photon beams, has been utilized as a "boost" technique at the time of surgical excision in a multimodal approach to treat radiosensitive cancers that cannot be completely resected or have a high risk of recurring in nearby tissues. When external beam IORT is delivered as a boost during surgical resection, the treatment augments conventional (traditional) external beam radiation therapy with reported fewer complications and fewer instances of recurrence in the treatment of specific cancer sites.

In addition, external beam IORT has been administered as the sole source of partial breast irradiation and an alternative to whole breast irradiation (WBI) in select individuals with early-stage breast cancer.  

Breast Cancer

External Beam IORT as Boost Radiotherapy for Breast Cancer

Reitsamer and colleagues (2004) attempted to determine the rate of local recurrences and the rate of distant metastases in 378 women with invasive breast cancer (T1 and T2 tumors) who were treated with breast-conserving surgery and postoperative radiation therapy to the whole breast (that is, WBI). From January 1996 to October 1998, group 1 participants (n=188) (n=128, T1 tumors; n=60, T2 tumors) were treated with breast-conserving surgery and postoperative WBI; additionally, an external-beam electron-boost (12 Gy in 2-Gy fractionation) was delivered to the tumor bed after surgical closure. From October 1998 to March 2001, group 2 (n=190) (n=130, T1 tumors; n=60, T2 tumors) participants were treated with breast-conserving surgery, IOERT (performed by linear accelerator with a single fractional dose of 9 Gy), and postoperative WBI. During a median follow-up period of 55.3 months in group 1 and 25.8 months in group 2, local recurrences were observed in 8 of 188 individuals (4.3%) in group 1 and no local recurrence was seen in group 2 (p=0.082). Distant metastases occurred in 15 of the 188 individuals (7.9%) in group 1 and in 2 of the 190 individuals (1.1%) in group 2 (p=0.09). The investigators concluded that immediate IOERT boost yielded excellent local control figures and appeared to be superior to conventional postoperative boost in a short-term follow-up period.

Sedlmayer and colleagues (2007) performed a pooled analysis of 1131 individuals treated for limited stage breast cancer with surgical resection and a single fractional boost dose of IOERT. WBI was prescribed with 50-54 Gy in single fractions of 1.7-2 Gy. Over 95% of the individuals received additional systemic therapy. At a median follow-up period of 52.3 months, only five in-breast recurrences were observed in the 1031 individuals available for analysis, yielding a local tumor control rate of 99.4%. At the 7-year follow-up, 964 individuals were alive without evidence of breast cancer. A total of 61 individuals developed metastases and 58 individuals died (25 from breast cancer and 6 from a secondary tumor). The actuarial disease-free survival (DFS) rates at 7 years were 88%, disease-specific survival and overall survival (OS) rates were 95.2% and 90.9%, respectively. The authors concluded that IOERT as boost therapy (with special attention to surgical margins) during breast-conserving surgery "guarantees optimal accuracy in dose delivery and thus outstanding local tumor control rates."

Subsequent studies report on the feasibility of using IORT as boost therapy to the primary tumor bed during breast-conserving surgery followed by WBI (Blank, 2010; Chua, 2011; Vaidya, 2011). Chua and colleagues (2011) reported on a single-arm prospective trial with results showing a comparatively high wound infection rate. The authors partially attributed the high rate of wound infection in participants at the study's cancer treatment center to "its more frequent post-treatment evaluations and the relatively low threshold for commencing antibiotics therapy for possible wound infection." Blank and colleagues (2010) reported a 5-year DFS rate of 81.0% and an OS of 91.3% in 197 participants who were treated with IORT during breast-conserving surgery as a boost followed by WBI. Local relapse-free survival (invasive cancers) at 3 and 5 years was 97.0%. At the 5-year follow-up, only 8 of 58 individuals (13.8%) had chronic skin toxicities, and 2 individuals (3.4%) had a marked increase in density (fibrosis III), while 62.0% had no or barely palpable fibrosis (0-I).

Vaidya and colleagues (2011) reported the long-term safety and efficacy results of targeted IORT as boost during breast-conserving surgery. A total of 300 cancers in 299 unselected participants underwent breast-conserving surgery and targeted IORT as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam WBI excluded the usual boost. An individualized case control (ICC) analysis computed the expected recurrences for the cohort by estimating the risk of recurrence for each participant using their characteristics and follow-up period. The treatment was reported as well-tolerated. At the median follow-up was 60.5 months (range, 10-122 months), 8 participants had ipsilateral recurrence, which was comparable with that seen in the boosted participants in the European Organization for Research and Treatment of Cancer (EORTC) study and the UK STAndardisation of breast RadioTherapy (START-B) study. In the ICC analysis of 242 participants, the authors estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. The authors concluded that lumpectomy with a targeted IORT boost combined with postoperative external beam radiation therapy (EBRT) resulted in a low local recurrence rate in a standard risk population.

In summary, the evidence in the peer-reviewed medical literature for external beam IORT using electron or photon radiotherapy as the sole source of boost therapy after breast-conserving therapy has demonstrated excellent local tumor control rates and acceptable side effects in the treatment of breast cancer.

The current National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines (CPGs) in Oncology® for breast cancer (V2.2017) do not include a discussion of external beam IORT as boost therapy to the primary tumor bed during surgical resection in the treatment of breast cancer.

External Beam IORT as Partial Breast Irradiation (PBI) for Breast Cancer

PBI is a localized form of radiation delivered after breast-conserving therapy (lumpectomy) to the part of the breast where the tumor was removed. IORT, which treats the partial breast with a single dose of radiation therapy using either low-energy x-rays or electrons, is most commonly delivered at the time of surgery. Intraoperative PBI after breast-conserving surgery has been proposed as an alternative to conventional WBI in appropriately selected individuals, offering several benefits, including reducing treatment time and sparing surrounding healthy tissue.

In 2017, the American Society for Radiation Oncology (ASTRO) updated an evidenced-based consensus statement (Correa, 2017) providing guidance on use of accelerated PBI (APBI), including new recommendations for PBI using IOERT or low-energy x-ray IORT in suitable candidates as an alternative to WBI in the treatment of early-stage breast cancer. The guidance recommends which individuals may be considered for intraoperative PBI, stating:

  1. Patients interested in cancer control equivalent to that achieved with WBI postlumpectomy for breast conservation should be counseled that in 2 clinical trials the risk of ipsilateral breast tumor recurrence (IBTR) was higher with IORT (higher quality of evidence, recommendation rated as "Strong," 97.5% Agreement).
  2. Electron beam IORT should be restricted to women with invasive cancer considered "suitable" for PBI based on the results of a multivariate analysis with median follow-up of 5.8 years (moderate quality of evidence [MQE] recommendation rated as "Strong," 100% Agreement).
  3. Low-energy x-ray IORT for PBI should be used within the context of a prospective registry or clinical trial, per ASTRO Coverage with Evidence Development (CED) statement. When used, it should be restricted to women with invasive cancer considered "suitable" for partial breast irradiation based on the data at the time of this review (MQE, recommendation rated as "Weak").

The updated consensus statement defines "suitable" candidates for PBI (that is, those with the lowest risk of IBTR) as follows:

ASTRO's consensus statement and recommendations for use of PBI in early-stage breast cancer considers expert opinion and published medical evidence from two large phase III clinical trials comparing WBI to PBI intraoperative radiotherapy with electrons (ELIOT trial) (Veronesi, 2013) or targeted intraoperative radiotherapy (TARGIT trial) (Vaidya, 2010; Vaidya, 2014) with low-energy x-rays (Intrabeam® , Carl Zeiss Meditec, Inc., Dublin, California) as the sole source of radiotherapy.

Veronesi and colleagues (2013) reported on the 5-year event rate of IBTR in outcomes of a randomized, controlled equivalence trial (ELIOT; NCT01849133) of 1305 women aged 48-75 years with early breast cancer suitable for breast-conserving therapy. Participants had a maximum tumor diameter of up to 2.5 centimeters assessed by preoperative imaging and after randomization, were stratified by clinical tumor size (that is, < 1.0 centimeter vs. 1.0-1.4 centimeter vs. ≥ 1.5 centimeter) to treatment with either external WBI (n=654) (50 Gy given in 25 fractions using tangential external beams, followed by a boost dose of 10 Gy in five fractions delivered using a direct external electron beam), or a single dose (21 Gy) of IOERT (n=651) administered to the tumor bed immediately after breast resection. The prespecified equivalence margin was local recurrence of 7.5% in the IOERT group, that is, local recurrence at 5 years in the IOERT group was within an equivalence margin and not significantly greater than in the WBI group. The primary endpoint was occurrence of IBTR; OS was a secondary outcome. All randomized participants were included in the intention-to-treat analysis. After a median follow-up of 5.8 years (interquartile range [IQR] 4.1-7.7), 35 participants in the IOERT group and 4 participants in the WBI group had IBTR (p<0•0001). The 5-year event rate for IBTR was 4.4% (95% confidence interval [CI], 2.7-6.1) in the IOERT group and 0.4% (0.0-1.0) in the WBI group (hazard ratio [HR] 9.33; 95% CI, 3.3-26.3). A total of 9 participants (5-year event rate, 1.0%; 95% CI, 0.2-1.9) in the IOERT group and 2 participants (5-year event rate, 0.3%; 95% CI, 0.0-0.8) in the WBI group developed axillary or other regional lymph node metastasis (p=0.03). The 5-year OS did not differ between the IOERT and WBI groups (34 deaths vs. 31 deaths, respectively; p=0.59). The 5-year OS was 96.8% (95% CI, 95.3-98.3) for the IOERT group and 96.9% (95% CI, 95.5-98.3) for the WBI group. Data was unavailable for side effects of radiotherapy for all participants. For those with available data (n=464 for IOERT; n=412 for WBI), significantly fewer skin side effects (erythema, dryness, hyperpigmentation, or pruritis) were reported in the IOERT group compared with the WBI group (p=0.0002); however, a higher incidence of radiologically determined fat necrosis was reported in the IOERT group (5%) compared with the WBI group (2%) (p=0.04). The investigators concluded that although the rate of IBTR in the IOERT group was within the prespecified equivalence margin, the rate was higher than with WBI at 5 years of follow-up; OS did not differ between the groups. The investigators stated that "the logical conclusion is that intraoperative radiotherapy with electrons should be restricted to suitable patients, once characteristics defining suitability have been identified."

Vaidya and colleagues (2010) reported on the feasibility, safety, and long-term efficacy of targeted IORT in the international, pragmatic, prospective, randomized, non-inferiority phase III trial (TARGIT-A) of women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery. Study participants were suitable for wide local excision that was unifocal on conventional examination and imaging. A preoperative diagnosis of lobular carcinoma was an exclusion from study participation. The primary outcome was local recurrence in the conserved breast. The pre-defined non-inferiority margin was an absolute difference of 2.5% in the primary endpoint. All randomized participants were included in the intention-to-treat analysis. A total of 1113 participants were randomly allocated to targeted IORT (low-energy x-ray) and 1119 were allocated to WBI (external beam). Of 996 participants who received the allocated treatment in the targeted IORT group, 854 (86%) received targeted IORT only and 142 (14%) received targeted IORT plus WBI. In the WBI group, 1025 (92%) participants received the allocated treatment. At 4 years, there were six local recurrences in the targeted IORT group and five in the WBI group. The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20% (95% CI, 0.53 to 2.71) in the targeted IORT and 0.95% (0.39 to 2.31) in the WBI group (difference between groups 0.25%, -1.04 to 1.54; p=0.41). The frequency of any complications and major toxicity was similar in the 2 groups (for major toxicity, targeted IORT, 37 [3.3%] of 1113 vs. WBI, 44 [3.9%] of 1119; p=0.44). Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3) was lower in the targeted IORT group (6 participants [0.5 %]) than in the WBI group (23 participants [2.1 %]; p=0.002). The investigators concluded that for select individuals with early breast cancer, a single dose of radiotherapy delivered at the time of surgery by use of targeted low-energy x-ray IORT could be considered as an alternative to WBI delivered over several weeks.

Sperk and colleagues (2012) reported the first analysis of long-term toxicities in women from a single center who participated in the TARGIT-A trial. In addition to the inclusion criteria as described in the Vaidya study (2010), participants in the WBI cohort included those with clear margins of less than 1 centimeter (a federal requirement in Germany). Between early 2002 and 2008, 305 participants were treated within TARGIT-A (Arm A: n=34 IORT, n=20 IORT + WBI for risk factors; Arm B WBI: n=55) or received IORT as a planned boost (control group: n=196). Assessment and grading of late radiation therapy toxicity was performed using the late effects of normal tissue-subjective objective management analytical (LENT-SOMA) scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p=0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBI vs. Arm B), fibrosis had a cumulative rate of 5.9% versus 37.5% versus 18.4%, respectively (38.2% IORT boost control group) at 3 years. No telangiectases were seen after IORT alone (0% Arm A IORT vs. 17.5% Arm A IORT + WBI vs. 17.7% Arm B). The HR of higher grade toxicity as first event was 0.46 (95% CI, 0.26-0.83) for Arm A IORT as compared to Arm B (p=0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). The authors concluded that IORT with 50 kilovolts (kV) x-rays demonstrated very low chronic skin toxicity rates and acceptable long-term results regarding toxicity and local control and is a safe and effective treatment of select individuals with breast cancer.

Vaidya and colleagues (2014) reported 5-year results for local recurrence and an analysis of OS comparing risk-adapted radiotherapy in women from the randomized, non-inferiority TARGIT-A trial (Vaidya, 2010). As previously described, women with early breast cancer were eligible if they were aged 45 years or older and suitable for wide local excision for invasive ductal carcinoma that was unifocal on conventional examination and imaging. Participants were randomly assigned in a 1:1 ratio to receive a risk-adapted approach using single-dose TARGIT (that is, a single dose of radiation to the tumor bed using targeted low-energy x-ray IORT) or WBI as per standard schedules over several weeks, with randomization blocks stratified by treatment center and by proposed timing of delivery of TARGIT. If the final pathology report showed unpredicted prespecified adverse features, then WBII was added to TARGIT, in which case TARGIT served as the tumor-bed boost. The core protocol defined three such features when WBI was recommended to supplement TARGIT within the experimental group: tumor-free margin smaller than 1 millimeter, extensive in-situ component, or unexpected invasive lobular carcinoma. According to the authors, the trial was "...a comparison of two policies: so called one-size-fits-all whole-breast radiotherapy versus individualised risk-adapted therapy - in which a proportion of patients who received TARGIT were also given EBRT if they were shown to have adverse tumour factors." The primary outcome was an absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2.5% at 5 years; prespecified analyses included outcomes as per timing of randomization in relation to lumpectomy. Secondary outcomes included complications and mortality. A total of 3451, 2020, and 1222 participants had a median follow-up of 2 years and 5 months, 4 years, and 5 years, respectively. The 5-year risk for local recurrence in the conserved breast following low-energy x-ray IORT was 3.3% (23 of 3375 participants; 95% CI, 2.1-5.1) compared to 1.3% in the WBI arm (11 of 3375 participants; 95% CI, 0.7-2.5) (p=0.042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had similar results as WBI: 2.1% (1.1-4.2) versus 1.1% (0.5-2.5; p=0.31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2.5% (TARGIT 5.4% [3.0-9.7] vs. WBI 1.7% [0.6-4.9]; p=0.069). Mortality from breast cancer was similar between groups (2.6% [1.5-4.3] for TARGIT vs. 1.9% [1.1-3.2] for WBI; p=0.56), although there were significantly fewer non-breast cancer deaths with TARGIT (1.4% [0.8-2.5] vs. 3.5% [2.3-5.2]; p=0.0086). Overall mortality was 3.9% (2.7-5.8) in the TARGIT group compared with 5.3% (3.9-7.3) in the WBI group (p=0.099). Similar wound-related complications were reported between groups, but grade 3 or grade 4 skin complications were significantly reduced with TARGIT (4 of 1720 vs. 13 of 1731; p=0.029).

Zur and colleagues (2016) evaluated the risk factors for early complications following breast-conserving surgery and IORT in 395 individuals treated for early breast cancer. IORT with Intrabeam was administered to individuals with breast cancer as part of an institutional clinical registry project at a single center in Israel. Clinical and treatment data and data regarding complications documented within 1 year of surgery were collected. Complications were documented in 108 (27.3%) individuals, including grade 3 or grade 4 complications in 5% of individuals. Infections, seroma, wound dehiscence, and bleeding and hematomas were diagnosed in 43 (10.8%), 40 (10.1%), 32 (8.1%), and 11(2.8%) individuals, respectively. Only 2 individuals had a small size skin necrosis. A total of 16 individuals with a seroma had a secondary complication; however, all complications were resolved. An increased risk of wound dehiscence and bleeding was associated with those individuals with diabetes mellitus and use of anticoagulants, respectively. The authors concluded that IORT following breast-conserving surgery for breast cancer is safe in appropriately selected individuals and "careful surgical technique and postoperative care is prudent." Although the rate of complications are reported as higher in individuals with early breast cancer following TARGIT at this single center, there are some limitations to drawing conclusions from this analysis. The study did not have a control group; therefore, it was not designed to address complication rates of individuals treated with breast-conserving surgery and TARGIT compared to individuals treated with WBI following breast-conserving surgery. It is unknown if the reported complication rates differed between surgeons with different levels of experience with the TARGIT procedure, as the analysis did not include a discussion of surgical techniques. As with any new surgical procedure, it would be expected that a reduction in complication rates would occur over time as the surgical volume increases and surgical techniques become standardized. The study authors acknowledged that individuals treated at a single center with the reported complications may have been influenced by surgical technique and post-operative care. A total of 208 (52.5%) participants were greater than 70 years of age, some participants had comorbid conditions, such as type 2 diabetes mellitus (n=111, 28.1%), and others were on anticoagulation therapy (n=133, 33.8%). Diabetes mellitus was associated with risk of wound dehiscence, and anticoagulant use was associated with risk of bleeding. The risk of complications, however, may be less if the individuals treated were younger and with fewer presurgical comorbidities and concurrent medications.

Corica and colleagues (2016) reported on longitudinal cosmesis and breast-related quality of life outcomes comparing participants randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT-IORT) (n=60) or external beam radiation therapy on the TARGIT-A trial (n=66). Longitudinal cosmesis and quality of life were collected from a subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure (postpathology reopening of the surgical wound). Participants completed a cosmetic assessment before radiation therapy and annually thereafter for at least 5 years. Participants also completed the combined European Organization for Research and Treatment of Cancer (EORTC) core questionnaire and Breast-Specific Module in addition to the Body Image after Breast Cancer Questionnaire at baseline and annually thereafter. The combined EORTC questionnaires were collected 3, 6, and 9 months after wide local excision. The participants reported an "excellent" to "good" cosmetic result more often than a "fair" to "poor" result for both treatment groups across all time points; however, multivariate longitudinal analysis did not reveal any statistically significant differences between treatment groups at any time point. The TARGIT-IORT participants reported better breast-related quality of life compared to external beam radiation participants, with statistically and clinically significant differences seen at month 6 and year 1, with external beam radiation therapy participants having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100-point scale) than TARGIT-IORT participants at these time points. At year 5, a significant difference in cosmesis was reported between the groups, as "excellent" to "good" scores were 68.4% for external beam radiation therapy and 90% for TARGIT-IORT (p=0.007). Study attrition was ruled out by sensitivity analysis as a potential cause of this difference. The authors suggested "…this evidence is important for clinicians and patients because it can facilitate the decision-making process regarding treatment options for early breast cancer treatable with breast-conserving therapy," as TARGIT-IORT may "better suit patient preferences for treatment."

The NCCN CPG for breast cancer (V2.2017) includes an updated algorithm for logoregional treatment of clinical stage I, IIA, or IIB disease or T3, N1 M0 invasive breast cancer. Following lumpectomy with surgical axillary staging with negative axillary nodes, the NCCN CPG includes a category 2A recommendation for "consideration of accelerated partial breast irradiation (APBI) in selected low-risk patients (PBI may be administered prior to chemotherapy)." The NCCN panel accepts ASTRO's updated APBI consensus statement guidelines which defines "suitable" candidates for APBI to be one of the following:

a)  50 years or older with invasive ductal carcinoma measuring ≤ 2 cm (T1 disease) with negative margin widths of ≥ 2 mm, no LVSI, ER-positive, and BRCA negative, or
b)  Low/intermediate nuclear grade, screen-detected DCIS measuring size ≤ 2.5 cm with negative margin widths of ≥ 3 mm.

The NCCN is currently updating the Discussion section of the CPG (V2.2017) to address the revised ASTRO recommendation.

Summary

The data in the peer-reviewed medical literature reporting outcomes of PBI with IOERT as an alternative to WBI following breast-conserving therapy for early-stage breast cancer consists of a randomized controlled trial (ELIOT) with a median of 5.8 years of follow-up (n=1305) (Veronesi, 2013). A very low 5-year occurrence rate of IBTR (approximately 1.5%) was reported among the study participants meeting ASTRO's "suitability" criteria (Correa, 2017), "…pointing out the importance of patient selection." Therefore, PBI with IOERT may be considered as a safe and effective radiotherapy option for select individuals in the treatment of early-stage breast cancer. It is recommended that individuals treated with IOERT "…undergo routine long-term follow-up for at least 10 years to screen for IBTR" (Correa, 2017).

The data in the peer-reviewed medical literature reporting outcomes of PBI with low-energy x-ray IORT as an alternative to WBI following breast-conserving therapy for early-stage breast cancer consists of 5-year results reporting local recurrence rates and an analysis of OS from the randomized, non-inferiority TARGIT-A trial (Vaidya, 2014). The overall median follow-up for TARGIT was 2.4 years (n=3451). The 5-year IBTR risk was 3.3% (23 of 3375 participants) in the low-energy x-ray IORT arm compared with 1.3% in the WBI arm (11 of 3375 participants) (p=0.42). There was no statistically significant difference in IBTR risk for individuals treated with IORT versus WBI in the TARGIT prepathology subgroup (2.1% [10 of 2234] with IORT vs. 1.1% [6 of 2234] with WBI). Therefore, use of low-energy x-ray IORT may be safe and effective when confined to use in individuals with the lowest risk of IBTR, specifically those in the "suitable" group.

Colorectal Cancers

IORT administered as boost therapy followed by postoperative EBRT and a multimodal treatment plan has been associated with improved local tumor control for individuals with colorectal cancer. Several retrospective studies and case series have demonstrated that adjuvant IORT has the potential to improve response rates with acceptable toxicities and improve survival with locally advanced colorectal cancer (Guo, 2012; Haddock, 2011).

Cantero-Muñoz and colleagues (2011) systematically reviewed the literature and suggested that IORT improves local control for individuals with locally advanced or recurrent colorectal cancer. Despite the heterogeneous populations included in the peer-reviewed case series and studies, the authors concluded that adding IORT to conventional treatment plans appeared to reduce the incidence of local recurrence in the surgical margins of the radiated areas by ten percent. Mirnezami and colleagues (2013) conducted a systematic review and meta-analysis on the use and outcomes after IORT for locally advanced or recurrent colorectal cancer. Fourteen prospective and 15 retrospective studies involving 3003 participants (n=1792 locally advanced disease; 1211 locally recurrent disease) received IORT. Comparative studies found a significant effect favoring IORT for improved local control, DFS, and OS. There was no increase in total (p=0.57), urologic (p=0.47), or anastomotic complications (p=0.98); however, increased wound complications were noted after IORT (p=0.049).

An American College of Radiology (ACR) Appropriateness Criteria® guideline (Konski, 2014) on recurrent rectal cancer states:

The NCCN CPG for colon cancer (V2.2017) includes a 2A recommendation for use of IORT stating, "IORT, if available may be considered for patients with T4 or recurrent cancers as an additional boost." For neoadjuvant/adjuvant therapy for selected rectal cancers, the NCCN CPG (V3.2017) recommends "IORT, if available, may be considered for very close or positive margins after resection, as an additional boost, especially for patients with T4 or recurrent cancers" (Alberda, 2014; Hahnloser, 2003; Hyngstrom, 2014; Willett, 2007). IORT should be considered as a treatment option if it can be delivered safely with surgical resection for pelvic/anastomotic recurrence (Dresen, 2008).

Pancreatic Adenocarcinoma

IORT has been used in individuals with pancreatic cancer or pelvic malignancies to rapidly and consistently control the associated visceral pain. In conjunction with pancreatic resection, a number of studies, retrospective case reviews, and systematic reviews of the literature suggest that IORT may improve resectability, local control, and disease control in this high risk population and for those with non-metastatic disease (Ashman, 2013; Cai, 2013; Chen, 2016; Jingu, 2012; Ogawa, 2010; Ruano-Ravina, 2008; Valentini, 2008). The NCCN CPG for pancreatic adenocarcinoma (V2.2017) states:

IORT is sometimes administered to patients with borderline resectable disease who have received maximal neoadjuvant therapy to sterilize close or involved margins at the time of surgery, although data in this setting are lacking. It is also sometimes used when a patient is found to be unresectable at the time of surgery and in cases of locally recurrent disease. Most studies of IORT in patients with locally advanced pancreatic cancer found that while local control may be improved, no change in survival is evident with use of IORT because of the high frequency at which metastatic disease develops. Some groups, however, believe that IORT can offer benefits in very carefully selected patients with non-metastatic disease.

The NCCN concludes that there is no clear established role for IORT in individuals with pancreatic cancer and it should only be performed at specialized centers.

Pelvic Cancers (Cervical and Uterine)

The NCCN CPG includes recommendations for the use of IORT for cervical (V1.2017) and uterine cancers (V1.2017). Recommendations for local/regional therapy (therapy for relapse) for cervical cancer include consideration of IORT after pelvic exenteration for central pelvic recurrent disease after initial radiation therapy (RT) (category 3 for IORT) (Tran, 2007), and after pelvic exenteration or resection for noncentral disease (category 3 for IORT). For individuals with isolated local recurrence (relapse) of uterine neoplasm that is confined to the pelvis, with or without prior external beam RT, the NCCN CPG (V1.2017) recommends surgical exploration of the pelvis and resection, with or without IORT (category 3 for IORT). For treating individuals with radiologically isolated vaginal/pelvic recurrence (relapse therapy) in individuals without prior RT exposure, options include surgery with IORT (category 3 for IORT) or tumor-directed RT with (or without) systemic therapy. Individuals with local recurrence who have had prior RT exposure can be treated with surgical resection with the option of IORT and/or systemic therapy (category 3 for IORT).

Soft Tissue Sarcomas

Sarcomas comprise a mixed group of rare solid tumors of mesenchymal cell origin with distinct clinical and pathological features, usually divided into two broad categories: 1) sarcomas of soft tissues (STS) (including fat, muscle, nerve and nerve sheath, blood vessels, and other connective tissues); and 2) sarcomas of bone. Surgery is the standard primary treatment for most sarcomas. The NCCN CPGs for STS (V2.2017) state if an individual cannot be treated with standard surgical intervention, preoperative radiation (or chemotherapy) should be considered as alternate treatment options. Surgery may be augmented with RT and chemotherapy pre- or postoperatively, with radiation boost with brachytherapy, IORT or an external RT (XRT) recommended for positive or close margins (Sadoski, 1993).

Retroperitoneal (RPS)/Intra-abdominal STS

As primary treatment for most individuals with RPS/intra-abdominal STS, the NCCN CPG (V2.2017) recommends preoperative radiotherapy (50 Gy external beam) followed by surgical resection with clips and consideration to boost therapy with IORT for positive margins (Gieschen, 2001; Pawlik, 2006; Pisters, 2003; Stucky, 2014). "Alternatively, IORT (10 to 12.5 Gy for microscopic residual disease and 15 Gy for gross residual disease) can be delivered immediately after resection to the area at risk, avoiding the uninvolved organs." For re-resection for individuals with macroscopically positive margins (R2 resection), options for postoperative RT include EBRT or IORT (10 Gy followed by EBRT). For resectable RPS/intra-abdominal STS in individuals who are not biopsied or biopsy is nondiagnostic, the NCCN CPG recommends surgery to obtain oncologically appropriate margins, with or without IORT. "IORT may be considered provided frozen section pathology can confidently demonstrate a non-GIST/non-desmoid histology."

Additional small case series have evaluated the use of IORT to the posterior margin to control microscopic residual disease and reduce local recurrence in individuals with surgically resected RPS (Yoon, 2010) and, in combination with surgical resection and EBRT for STS (Niewald, 2009). The authors state these treatment strategies minimize radiation-related morbidity, reduce local recurrence, particularly in individuals with primary disease, and yield survival data well within the range of the results reported in the peer-reviewed literature.

An ongoing prospective, one-arm phase II clinical trial (RETROWTS; NCT01566123) is examining preoperative radiotherapy combining neoadjuvant dose-escalated IMRT (50-56 Gy) followed by surgery with IORT (10-12 Gy) in individuals with high-risk, marginally resectable RPS. The primary outcome measure is the local control rate after 5 years. Preliminary results suggest promising local control and OS rates (Roeder, 2014). The estimated study completion date is February 2020.

STS of the Extremity, Trunk, Head and Neck

Tran and colleagues (2006) suggested IORT provided excellent local control with limited acute toxicities for extremity STS when used as a boost to EBRT. The investigators noted that radiation of extremity lesions presents particular challenges with the significant risk of toxicities. Gross total resections were achieved in all 17 individuals. Two individuals experienced locoregional relapses, 6 individuals recurred at metastatic sites, and 1 individual died without recurrence. At 36 months, estimates for locoregional control, DFS, and OS were 86%, 50%, and 78%, respectively.

Call and colleagues (2014) reported long-term outcomes in 61 individuals with upper extremity STS treated with EBRT, surgery, and IORT, with or without adjuvant chemotherapy. The 10-year local control and OS rates were 88% and 58%, respectively. Following margin-negative (R0) and margin-positive (R1 and R2 resections), the 10-year local control rates were 89% and 86%, respectively. Limb preservation was achievable for most participants. Severe treatment-related toxicities were noted in 7% of participants.

Calvo and colleagues (2014) retrospectively investigated the long-term outcomes of locally recurrent STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases in 103 individuals who underwent radical surgery and IOERT (median dose, 12.5 Gy). A total of 62% of participants also received EBRT (median dose, 50 Gy). With a median follow-up of 57 months (range, 2-311 months), 5-year local control was 60%. The 5-year IORT in-field control, DFS, and OS were 73%, 43%, and 52%, respectively (p=0.03). However, given the high risk of distant metastases with STS, DFS remained modest.

Roeder and colleagues (2016) retrospectively analyzed outcomes of 183 individuals treated with IOERT, postoperative EBRT, and limb sparing surgery in the treatment of extremity STS. A total of 80% of the cases had STS located in the lower limb. Stage at presentation was: I: 6%; IIa: 25%; IIb: 21%; III: 42%; and, IV: 7%. The majority of cases showed high-grade lesions (grade 1: 5%; grade 2: 31%; and grade 3: 64%). IOERT was applied to the tumor bed (median 15 Gy) and was preceded (9%) or followed (91%) by EBRT (median 45 Gy) in all individuals. The median follow-up was 64 months (78 months in survivors); surgery was complete in 68%, while 32% had microscopic residual disease. The 5- and 10-year local control rates were 86% and 84%, respectively; and, local control was significantly higher in primary compared to recurrent disease and tended to be higher after complete resection. The estimated 5- and 10-year distant control rates were 68% and 66%, while corresponding OS was 77% and 66%, respectively; OS was significantly affected by grading and stage. Severe postoperative complications and late toxicities were observed in 19% and 20% of individuals, respectively. The rate of limb preservation was 95% with "good function" in 83% of cases.

Sole and colleagues (2016) assessed long-term outcomes and toxicity of IOERT in the management of pediatric subjects with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). A total of 71 (EWS, n=37 [52%]; RMS n=34 [48%]) children underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%). Local control, OS, and DFS were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. After a median follow-up of 72 months (range, 4-310 months), the 10-year local control, DFS, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis (and after adjustment for other covariates), disease status (p=0.04 and p=0.05) and R1 margin status (p<0.01 and p=0.04) remained significantly associated with local control and OS, Severe chronic toxicity events (all grade 3) were reported in 9 (13%) children.

The NCCN CPG for radiation therapy for STS of the extremity, trunk, head and neck (V2.2017) recommends IORT (10 to 12.5 Gy for microscopic residual disease and 15 Gy for gross residual disease) delivered as boost  radiotherapy for positive margins immediately after surgical resection with clips to the area at risk to avoid the uninvolved organs. For those individuals who have not received preoperative radiotherapy, postoperative radiotherapy options following surgery with clips include EBRT (50 Gy), IORT (10 to 16 Gy), or brachytherapy. EBRT following IORT or brachytherapy is delivered to the target volume to a total dose of 50 Gy, after surgical healing is complete (3 to 8 weeks).

IORT for Other Cancers

The peer-reviewed literature evaluating the role of IORT in the treatment of other types of cancers consists of retrospective case series and early phase I/II randomized controlled trials of varying size and duration. These studies analyze the impact of IORT after surgical resection and as adjuvant radiotherapy on OS rates, disease reoccurrence or tumor progression, and early and late toxicities.  

Gastric Cancer

Drognitz and colleagues (2008) retrospectively analyzed the impact of IORT in a phase II trial of long-term survival in individuals (n=84) with resectable gastric cancer. A total of 61 individuals with gastric neoplasm who underwent gastrectomy or subtotal resection with IORT were retrospectively matched with 61 individuals without IORT (IORT[-] group) for Union Internationale Contre le Cancer (UICC) stage, age, histologic grading, extent of surgery, and level of lymph node dissection. Mean follow-up was 4.8 years and 5 years in the IORT(+) group and IORT(-) group, respectively. The 5-year OS rate was 58% in the IORT(+) group compared to 59% in the IORT(-) group (p=0.99). Subgroup analysis showed no impact of IORT on the 5-year survival rate for those with UICC Stages I/II (76% vs. 80%; p=0.87) and III/IV (21% vs. 14%, IORT[+] vs. IORT[-] group; p=0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT(+) and IORT(-) group, respectively. Total surgical complications were more common in the IORT(+) than IORT(-) group (44.3% vs. 19.7%; p<0.05). The locoregional tumor recurrence rate was 9.8% in the IORT(+) group. The investigators concluded that the use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in individuals with curable gastric cancer.

Calvo and colleagues (2013b) reported long-term outcomes in individuals with resectable locally advanced gastric adenocarcinoma treated with IORT. A total of 32 individuals with primary gastric adenocarcinoma were treated with curative resection and lymphadenectomy for stage II disease confined to the locoregional area (n=15) or stage III disease (n=17). IORT was administered over the celiac axis and peripancreatic nodal areas. A total of 16 participants (50%) also received adjuvant treatment (EBRT, chemoradiation, or chemotherapy alone). At the median follow-up of 40 months, locoregional recurrence was observed in 5 (16%) participants. The OS at 5 years was 54% (95% CI: 48.6 to 60.6 months). Postoperative mortality and complications were 6% (n=2) and 19% (n=6), respectively.

Yu and colleagues (2015) performed a meta-analysis of studies involving the use of IORT for resectable gastric cancer. The impact of adjuvant IORT on OS and locoregional control were described using HRs and extracted directly from the original studies or calculated from survival curves. Data from four studies provided OS data, identifying that IORT had no significant impact on OS (HR 0.97; 95% CI, 0.75 to 1.26; p=0.837). In three studies that tested the efficacy of IORT for OS in a subgroup of individuals with stage III disease, there was a significantly improved OS (HR 0.60; 95% CI, 0.40 to 0.89; p=0.011). Significant improvement in locoregional control was observed in four studies that provided such data (HR 0.40; 95% CI, 0.26 to 0.62; p<0.001). The authors concluded that this meta-analysis showed a statistically significant locoregional control benefit with the addition of IORT in individuals with resectable gastric cancer.

The current NCCN CPG for radiation therapy for gastric carcinoma (V1.2017) suggests the feasibility of IORT in the treatment of individuals with potentially resectable gastric cancer when used in combination with preoperative chemoradiation. No other recommendations were discussed beyond the results of one pilot study (Lowy, 1999).

Head and Neck Cancer

Several studies have evaluated the possible role of IORT as palliative treatment of recurrent head and neck cancer. Perry and colleagues (2010) reported on a small group of individuals (n=34) with recurrent head and neck cancer who received high-dose-rate IORT. Although the results were reported as encouraging, only 8 individuals (24%) were disease-free at a median follow-up of 23 months (range, 6-54 months). The authors suggested these were acceptable rates of treatment-related morbidity for individuals with recurrent head and neck cancer; however, longer follow-up with a larger cohort of subjects is needed to fully assess the benefit of this procedure.

Zeidan and colleagues reported on two case series of IORT for head and neck cancer. The first case series (n=231) reviewed data collected over a 14 year time period on the use of IORT for individuals with advanced cervical node metastasis resulting from head and neck malignancies (Zeidan, 2011). The OS at 1, 3, and 5 years after surgery and IORT was 58%, 34%, and 26%, respectively. Recurrence-free survival (RFS) at 1, 3, and 5 years was 66%, 55%, and 49%, respectively. Disease recurrence was documented in 83 (42.8%) individuals (n=38 regional; n=20 local; and n=25 distant failures). The authors concluded that IORT resulted in effective local disease control at acceptable levels of toxicity. The results indicate the need for a phase III trial comparing outcomes for individuals with cervical metastasis treated with or without IORT. The second publication (Zeidan, 2012) reviewed the authors' experience with the use of IORT for primary or recurrent cancer of the parotid gland. Over a similar 14 year period, 96 individuals were treated with gross total resection and IORT for primary or recurrent cancer of the parotid gland. Of these individuals, 33 had previously undergone EBRT as a component of definitive therapy, 34 had positive margins after surgery, and 40 had perineural invasion. IORT was administered as a single fraction of 15 or 20 Gy. The median follow-up period was 5.6 years. Local, regional, or distant recurrence was experienced in 1, 19, and 12 individuals, respectively. The RFS rate at 1, 3, and 5 years was 82%, 69%, and 65%, respectively. The 1, 3, and 5 year OS survival rates after surgery and IORT were 88%, 66%, and 56%, respectively. The authors concluded that IORT resulted in local disease control at acceptable levels of toxicity and should be considered for individuals with primary or recurrent cancer of the parotid gland. This retrospective cohort study is limited in drawing conclusions as it was insufficiently large to determine the treatment benefit attributable to IORT alone. Most individuals received different types of adjuvant chemotherapy and radiation therapy before and/or after IORT. In addition, the study omitted individuals with records unavailable for the analysis, thus introducing potential bias into the results. Additional study is needed in the form of a randomized controlled trial to determine the treatment benefit of IORT for primary or recurrent cancer of the parotid gland. 

Summary for Other Types of Cancers

The current peer-reviewed published literature includes small, retrospective studies or early phase clinical trials with preliminary results on the efficacy and safety of IORT as boost RT for individuals with aggressive fibromatosis (Roeder, 2010), squamous cell carcinoma of the anus (Hallemeier, 2014), central nervous system (brain) cancer (Nemoto, 2002), early-stage oral cancer (Rutkowski, 2010), glioblastoma multiforme (Giordano, 2014), non-small cell lung cancer (Jaske, 2007), recurrent neuroblastoma (Rich, 2011), post-radical prostatectomy for localized (Saracino, 2008) or locally advanced prostate cancer (Krengli, 2010), and locoregionally recurrent or locoregionally advanced primary renal cell cancer (RCC) (Calvo, 2013a; Hallemeier, 2012).

Paly and colleagues (2014) analyzed outcomes in 98 individuals with advanced or locally recurrent RCC treated with IORT during nephrectomy at nine different institutions during the period of 1985 to 2010. In addition to IORT, EBRT was given to 27% preoperatively and to 35% postoperatively. The median follow-up time was 3.5 years for surviving participants. The 5-year OS for participants with advanced disease, disease-specific survival (DSS), and DFS were 37%, 41% and 39%, respectively. For locally recurrent disease, the 5-year OS, DSS, and DFS were 55%, 60%, and 52%. For locally recurrent tumors, positive margin status (HR 2.6; p=0.01) was associated with decreased OS.

In summary, further randomized controlled trials are needed to determine the safety and efficacy of IORT in combination with other radiation therapy techniques, with or without chemotherapy and surgical resection, in the treatment of other neoplasms. These trials should include data that evaluates overall treatment outcomes including early and late toxicity and patterns of tumor reoccurrence.

Background/Overview

IORT may be useful at the time of surgical excision to treat localized radiosensitive cancers that cannot be completely removed or that have a high risk of recurring in nearby tissues. The success of IORT is dependent on appropriate selection of individuals and the use of other adjuvant therapies in the treatment of tumor sites.

IORT or intraoperative radiotherapy is designed to increase the intensity of radiation delivered directly to tumors at the time of surgery to enhance local tumor control. Most individuals are concurrently treated with high dose external beam photon irradiation. The tumor volume and associated tissues at risk for micrometastatic spread are directly visualized at operation. IORT is delivered directly to the tumor volume as "boost" therapy where normal or uninvolved tissues are not exposed to radiation because they are shielded from the treatment field. Further benefits of IORT are the use of small treatment volumes, complete skin sparing, and reduction of radiation time.

IORT may be used to treat the partial breast with a single dose of radiation (that is, PBI) using either low-energy x-ray or electrons (that is, IOERT) delivered at the time of surgery as an alternative to WBI post-lumpectomy for breast conservation. IORT with PBI is restricted to use in select (suitable) individuals with breast cancer, and has the benefits of reducing treatment time and sparing healthy tissue.

IORT is performed with applicators and cones that attach to the treatment head of high-energy medical linear accelerators designed to direct radiation to defined surface structures. IORT can be delivered with photon beams (x-rays or gamma rays) or electron beams (IOERT) produced by a linear accelerator generally used for EBRT. If available, a specialized mobile accelerator can be transported any day of use to almost any location within a hospital setting. IOERT is selected to treat accessible sites because the set-up and treatment time are both shorter and a greater depth dose can be achieved. However, the use of IOERT may be unsuitable for treating sites such as inferior, lateral or sub-pelvic locations, anterior abdominal wall, sub-diaphragmatic areas, anterior or lateral interior chest wall, and narrow cavities like the paranasal sinuses because these areas are poorly accessible to the electron beam which travels only in a straight line with a finite applicator diameter.

Definitions

Boost radiation: An additional dose of radiation (dose escalation) to a reduced size radiation field.

Brachytherapy (also known as internal radiation): A type of radiation treatment used to stop the growth of cancer cells by implanting radioactive material directly into the tumor or into the surrounding tissues. (Also see: THER-RAD.00001 Brachytherapy for Oncologic Indications).

Breast-conserving surgery: A treatment alternative to mastectomy for early stage breast cancer consisting of tumor removal (lumpectomy) followed by external beam radiation to the whole breast (WBI).

Ductal carcinoma in situ (DCIS): A noninvasive condition in which abnormal cells are found in the lining of a breast duct. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive cancer and spread to other tissues (NCI, 2017).

External beam radiation therapy (EBRT): A form of radiation therapy (such as, three dimensional conformal radiation therapy [3D-CRT], intensity modulated radiation therapy [IMRT], and image guided radiation therapy [IGRT]) used to stop the growth of cancer cells. A linear accelerator directs a photon (x-ray or gamma ray) or electron beam (particle radiation) from outside the body through normal or healthy body tissue to reach the cancer. The radiation is typically given 5 days a week for a period of 3 to 8 weeks.

Head and neck cancers: Cancers arising from the oral cavity and lips, larynx, hypopharynx, oropharynx, nasopharynx, paranasal sinuses and nasal cavity, salivary glands, mucosal melanoma and occult primaries in the head and neck region.

Intraoperative electron (beam) radiation therapy (IOERT): An IORT technique that uses an electron beam applicator suitable for shorter treatment time and greater depth of dosage. IOERT is delivered as a high energy source (typically up to 12 megavolts [mV]) applied through cylindrical applicators of various diameters and terminal angles.

Intraoperative photon (beam) IORT: An IORT technique that uses low energy x-rays or gamma rays (typically up to 50 kilovolts [kV]) administered through spherical applicators of various diameters.

Intraoperative radiation therapy (IORT): The delivery of a single fractional dose of radiation administered directly to the tumor bed (confirmed target) during surgery.

Partial breast irradiation (PBI): Also known as limited field radiation therapy, accelerated partial breast irradiation (APBI). A type of radiation therapy confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery. PBI may use internal or external sources of radiation.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

CPT

 

77424

Intraoperative radiation treatment delivery, x-ray, single treatment session

77425

Intraoperative radiation treatment delivery, electrons, single treatment session

77469

Intraoperative radiation treatment management

 

 

ICD-10 Diagnosis

 

C18.0-C20

Malignant neoplasm of colon, rectosigmoid junction, rectum

C21.0-C21.8

Malignant neoplasm of anus and anal canal

C25.0-C25.9

Malignant neoplasm of pancreas

C46.1

Kaposi’s sarcoma of soft tissue

C48.0-C48.8

Malignant neoplasm of retroperitoneum and peritoneum

C49.0-C49.9

Malignant neoplasm of other connective and soft tissues

C50.011-C50.929

Malignant neoplasm of breast

C53.0-C55

Malignant neoplasm of cervix uteri, corpus uteri, part unspecified

C56.1-C56.9

Malignant neoplasm of ovary

C57.00-C57.9

Malignant neoplasm of other and unspecified female genital organs

C58

Malignant neoplasm of placenta

C69.60-C69.62

Malignant neoplasm of orbit [when specified as soft tissue sarcoma]

C76.3

Malignant neoplasm of pelvis

C77.5

Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes

C78.5

Secondary malignant neoplasm of large intestine and rectum

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.89

Secondary malignant neoplasm of other digestive organs (pancreas)

C79.60-C79.62

Secondary malignant neoplasm of ovary

C79.81

Secondary malignant neoplasm of breast

C79.82

Secondary malignant neoplasm of genital organs

D01.0-D01.2

Carcinoma in situ of colon, rectosigmoid junction, rectum

D01.7

Carcinoma in situ of other specified digestive organs (pancreas)

D05.00-D05.92

Carcinoma in situ of breast

D06.0-D06.9

Carcinoma in situ of cervix uteri

D07.39

Carcinoma in situ of other female genital organs

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services may also be Medically Necessary when criteria are met:

CPT

 

19294

Preparation of tumor cavity, with placement of a radiation therapy applicator for intraoperative radiation therapy (IORT) concurrent with partial mastectomy

 

 

ICD-10 Procedure

 

DD053Z0-DD073Z0

Beam radiation of colon, rectum using electrons, intraoperative [includes codes DD053Z0, DD073Z0]

DDY5CZZ-DDY8CZZ

Intraoperative radiation therapy (IORT) of colon, rectum, anus [includes codes DDY5CZZ, DDY7CZZ, DDY8CZZ]

DF033Z0

Beam radiation of pancreas using electrons, intraoperative

DFY3CZZ

Intraoperative radiation therapy (IORT) of pancreas

D7063Z0-D7073Z0

Beam radiation of abdomen lymphatics, pelvis lymphatics using electrons, intraoperative [includes codes D7063Z0, D7073Z0]

DU003Z0-DU023Z0

Beam radiation of ovary, cervix, uterus using electrons, intraoperative [includes codes DU003Z0, DU013Z0, DU023Z0]

DUY0CZZ-DUY2CZZ

Intraoperative radiation therapy (IORT) of ovary, cervix, uterus [includes codes DUY0CZZ, DUY1CZZ, DUY2CZZ]

DM003Z0-DM013Z0

Beam radiation of breast using electrons, intraoperative [left or right; includes codes DM003Z0, DM013Z0]

DH023Z0-DH0B3Z0

Beam radiation of skin using electrons, intraoperative [by body area; includes codes DH023Z0, DH033Z0, DH043Z0, DH063Z0, DH073Z0, DH083Z0, DH093Z0, DH0B3Z0]

DW013Z0-DW063Z0

Beam radiation using electrons, intraoperative [by body area; includes codes DW013Z0, DW023Z0, DW033Z0, DW063Z0]

 

 

ICD-10 Diagnosis

 

 

All diagnoses

When services are Investigational and Not Medically Necessary:
For the ICD-10 procedure codes listed above when criteria are not met, for the following procedure codes, or when the code describes a procedure indicated in the Position Statement as investigational and not medically necessary.

 

ICD-10 Procedure

 

 

For all other intraoperative electron beam radiation or IORT procedure codes, including the following:

D0003Z0-D0073Z0

Central and peripheral nervous system, IOERT: D0003Z0, D0013Z0, D0063Z0, D0073Z0

D7003Z0-D7083Z0

Lymphatic and hematologic, IOERT: D7003Z0, D7013Z0, D7023Z0, D7033Z0, D7043Z0, D7053Z0, D7083Z0

D8003Z0

Eye, IOERT: D8003Z0

D9003Z0-D90F3Z0

Ear, nose mouth and throat, IOERT: D9003Z0, D9013Z0, D9033Z0, D9043Z0, D9053Z0, D9063Z0, D9073Z0, D9083Z0, D9093Z0, D90B3Z0, D90D3Z0, D90F3Z0

D9Y4CZZ-D9YCCZZ

Ear, nose mouth and throat, IORT: D9Y4CZZ, D9YBCZZ, D9YDCZZ, D9YCCZZ

DB003Z0-DB083Z0

Respiratory, IOERT: DB003Z0, DB013Z0, DB023Z0, DB053Z0, DB063Z0, DB073Z0, DB083Z0

DD003Z0-DD043Z0

Gastrointestinal, IOERT (esophagus, stomach, small intestine): DD003Z0, DD013Z0, DD023Z0, DD033Z0, DD043Z0

DDY1CZZ-DDY4CZZ

Gastrointestinal, IORT ( stomach, small intestine): DDY1CZZ, DDY2CZZ, DDY3CZZ, DDY4CZZ

DF003Z0-DF023Z0

Hepatobiliary, IOERT (liver, gallbladder, bile ducts): DF003Z0, DF013Z0, DF023Z0

DFY0CZZ-DFY2CZZ

Hepatobiliary, IORT );liver, gallbladder, bile ducts): DFY0CZZ, DFY1CZZ, DFY2CZZ

DG003Z0-DG053Z0

Endocrine, IOERT: DG003Z0, DG013Z0, DG023Z0, DG043Z0, DG053Z0

DP003Z0-DP0C3Z0

Musculoskeletal, IOERT: DP003Z0, DP023Z0, DP033Z0, DP043Z0, DP053Z0, DP063Z0, DP073Z0, DP083Z0, DP093Z0, DP0B3Z0, DP0C3Z0

DT003Z0-DT033Z0

Urinary, IOERT: DT003Z0, DT013Z0, DT023Z0, DT033Z0

DTY0CZZ- DTY3CZZ

Urinary, IORT: DTY0CZZ, DTY1CZZ, DTY2CZZ, DTY3CZZ

DV003Z0-DV013Z0

Prostate, testis IOERT: DV003Z0, DV013Z0

DVY0CZZ

Prostate IORT: DVY0CZZ

DW043Z0-DW053Z0

Anatomical, IOERT: DW043Z0, DW053Z0

 

 

ICD-10 Diagnosis

 

 

All diagnoses

References

Peer Reviewed Publications:

  1. Alberda WJ, Verhoef C, Nuyttens JJ, et al. Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2014; 88(5):1032-1040.
  2. Blank E, Kraus-Tiefenbacher U, Welzel G, et al. Single-center long-term follow-up after intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage x-rays. Ann Surg Oncol. 2010; 17(3):352-358.
  3. Cai S, Hong TS, Goldberg SI, et al. Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. Cancer. 2013; 119(23):4196-4204.
  4. Call JA, Stafford SL, Petersen IA, et al. Use of intraoperative radiotherapy for upper-extremity soft-tissue sarcomas: analysis of disease outcomes and toxicity. Am J Clin Oncol. 2014; 37(1):81-85.
  5. Calvo FA, Sole CV, Cambeiro M, et al. Prognostic value of external beam radiation therapy in patients treated with surgical resection and intraoperative electron beam radiation therapy for locally recurrent soft tissue sarcoma: a multicentric long-term outcome analysis. Int J Radiat Oncol Biol Phys. 2014; 88(1):143-150.
  6. Calvo FA, Sole CV, Martinez-Monge R, et al. Intraoperative EBRT and resection for renal cell carcinoma: twenty-year outcomes. Strahlenther Onkol. 2013a; 189(2):129-136.
  7. Calvo FA, Sole CV, Obregon R, et al. Intraoperative radiotherapy for the treatment of resectable locally advanced gastric adenocarcinoma: topography of locoregional recurrences and long-term outcomes. Clin Transl Onco. 2013b; 15(6):443-449.
  8. Cantero-Muñoz P, Urién MA, Ruano-Ravina A. Efficacy and safety of intraoperative radiotherapy in colorectal cancer: a systematic review. Cancer Lett. 2011; 306(2):121-133.
  9. Chen Y, Che X, Zhang J, et al. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer: retrospective cohort study, 7-year experience with 247 patients at the National Cancer Center in China. Medicine (Baltimore). 2016; 95(38):e4861.
  10. Chua BH, Henderson MA, Milner AD. Intraoperative radiotherapy in women with early breast cancer treated by breast-conserving therapy. ANZ J Surg. 2011; 81(1-2):65-69.
  11. Corica T, Nowak AK, Saunders CM, et al. Cosmesis and breast-related quality of life outcomes after intraoperative radiation therapy for early breast cancer: a substudy of the TARGIT-A Trial. Int J Radiat Oncol Biol Phys. 2016; 96(1):55-64.
  12. Dresen RC, Gosens MJ, Martijn H, et al. Radical resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer. Ann Surg Oncol. 2008; 15(7):1937-1947.
  13. Drognitz O, Henne K, Weissenberger C, et al. Long-term results after intraoperative radiation therapy for gastric cancer. Int J Radiat Oncol Biol Phys. 2008; 70(3):715-721.
  14. Gieschen HL, Spiro IJ, Suit HD, et al. Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma. Int J Radiat Oncol Biol Phys. 2001; 50(1):127-131.
  15. Giordano FA, Brehmer S, Abo-Madyan Y, et al. INTRAGO: intraoperative radiotherapy in glioblastoma multiforme - a phase I/II dose escalation study. BMC Cancer. 2014; 14:992.
  16. Guo S, Reddy CA, Kolar M, et al. Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience. Radiat Oncol. 2012; 7:110.
  17. Haddock MG, Miller RC, Nelson H, et al. Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer. Int J Radiat Oncol Biol Phys. 2011; 79(1):143-150.
  18. Hahnloser D, Haddock MG, Nelson H. Intraoperative radiotherapy in the multimodality approach to colorectal cancer. Surg Oncol Clin N Am. 2003; 12(4):993-1013, ix.
  19. Hallemeier CL, Choo R, Davis BJ, et al. Long-term outcomes after maximal surgical resection and intraoperative electron radiotherapy for locoregionally recurrent or locoregionally advanced primary renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2012; 82(5):1938-1943.
  20. Hallemeier CL, You YN, Larson DW, et al. Multimodality therapy including salvage surgical resection and intraoperative radiotherapy for patients with squamous-cell carcinoma of the anus with residual or recurrent disease after primary chemoradiotherapy. Dis Colon Rectum. 2014; 57(4):442-448.
  21. Hyngstrom JR, Tzeng CW, Beddar S, et al. Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience. J Surg Oncol. 2014; 109(7):652-658.
  22. Jaske G, Kapp K, Geyer E, et al. IORT and external beam irradiation (EBI) in clinically stage I-II NSCLC patients with severely compromised pulmonary function: a 52-patient single-institutional experience. Strahlenther Onkol. 2007; 183(2):24-25.
  23. Jingu K, Tanabe T, Nemoto K, et al. Intraoperative radiotherapy for pancreatic cancer: 30-year experience in a single institution in Japan. Int J Rad Oncol Biol Phys. 2012; 83(4):e507-e571.
  24. Krengli M, Terrone C, Ballarè A, et al. Intraoperative radiotherapy during radical prostatectomy for locally advanced prostate cancer: technical and dosimetric aspects. Int J Radiat Oncol Biol Phys. 2010; 76(4):1073-1077.
  25. Lowy AM, Mansfield PF, Leach SD, et al. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999; 229(3):303-308.
  26. Mirnezami R, Chang GJ, Das P, et al. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol. 2013; 22(1):22-35.
  27. Nemoto K, Ogawa Y, Matsushita H, et al. Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas. BMC Cancer. 2002; 2:1-5.
  28. Niewald M, Fleckenstein J, Licht N, et al. Intraoperative radiotherapy (IORT) combined with external beam radiotherapy (EBRT) for soft-tissue sarcomas--a retrospective evaluation of the Homburg experience in the years 1995-2007. Radiat Oncol. 2009; 4:32.
  29. Ogawa K, Karasawa K, Ito Y, et al. Intraoperative radiotherapy for resected pancreatic cancer: a multi-institutional retrospective analysis of 210 patients. Int J Radiat Oncol Biol Phys. 2010; 77(3):734-742.
  30. Paly JJ, Hallemeier CL, Biggs PJ, et al. Outcomes in a multi-institutional cohort of patients treated with intraoperative radiation therapy for advanced or recurrent renal cell carcinoma. Int J Radiat Oncol Biol Phys. 2014; 88(3):618-623.
  31. Pawlik TM, Pisters PW, Mikula L, et al. Long-term results of two prospective trials of preoperative external beam radiotherapy for localized intermediate- or high-grade retroperitoneal soft tissue sarcoma. Ann Surg Oncol. 2006; 13(4):508-517.
  32. Perry DJ, Chan K, Wolden S, et al. High-dose-rate intraoperative radiation therapy for recurrent head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010; 76(4):1140-1146.
  33. Pisters PW, Ballo MT, Fenstermacher MJ, et al. Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma. J Clin Oncol. 2003; 21(16):3092-3097.
  34. Reitsamer R, Peintinger F, Kopp M, et al. Local recurrence rates in breast cancer patients treated with intraoperative electron-boost radiotherapy versus postoperative external-beam electron-boost irradiation. A sequential intervention study. Strahlenther Oncol. 2004; 180(1):38-44.
  35. Reitsamer R, Sedlmayer F, Koop M, et al. Concepts and techniques of intraoperative radiotherapy for breast cancer. Breast Cancer. 2008; 15(1):40-46.
  36. Rich BS, McEvoy MP, LaQuaglia MP, Wolden SL. Local control, survival, and operative morbidity and mortality after re-resection, and Intraoperative radiation therapy for recurrent or persistent primary high-risk neuroblastoma. J Pediatr Surg. 2011; 46(1):97-102.
  37. Roeder F, Lehner B, Saleh-Ebrahimi L, et al. Intraoperative electron radiation therapy combined with external beam radiation therapy and limb sparing surgery in extremity soft tissue sarcoma: a retrospective single center analysis of 183 cases. Radiother Oncol. 2016; 119(1):22-29.
  38. Roeder F, Timke C, Oertel S, et al. Intraoperative electron radiotherapy for the management of aggressive fibromatosis. Int J Radiat Oncol Biol Phys. 2010; 76(4):1154-1160.
  39. Roeder F, Ulrich A, Habl G, et al. Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis. BMC Cancer. 2014; 14:617.
  40. Ruano-Ravina A, Almazán Ortega R, Guedea F. Intraoperative radiotherapy in pancreatic cancer: a systematic review. Radiother Oncol. 2008; 87(3):318-325.
  41. Rutkowski T, Wygoda A, Hutnik M, et al. Intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy: treatment feasibility and preliminary results. Strahlenther Onkol. 2010; 186(9):496-501.
  42. Sadoski C, Suit HD, Rosenberg A, et al. Preoperative radiation, surgical margins, and local control of extremity sarcomas of soft tissues. J Surg Oncol. 1993; 52(4):223-230.
  43. Saracino B, Gallucci M, De Carli P. et al. Phase I-II study of intraoperative radiation therapy (IORT) after radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 71(4):1049-1056.
  44. Sedlmayer F, Fastner G, Merz F, et al. IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: results of an ISIORT pooled analysis. Strahlenther Onkol. 2007; 183(2):32-44.
  45. Sole CV, Calvo FA, Polo A, et al. Intraoperative electron-beam radiation therapy for pediatric Ewing sarcomas and rhabdomyosarcomas: long-term outcomes. Int J Radiat Oncol Biol Phys. 2015; 92(5):1069-1076.
  46. Sperk E, Welzel G, Keller A, et al. Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A. Breast Cancer Res Treat. 2012; 135(1):253-260.
  47. Stucky CC, Wasif N, Ashman JB, et al. Excellent local control with preoperative radiation therapy, surgical resection, and intra-operative electron radiation therapy for retroperitoneal sarcoma. J Surg Oncol. 2014; 109(8):798-803.
  48. Tran QN, Kim AC, Gottschalk AR, et al. Clinical outcomes of intraoperative radiation therapy for extremity sarcomas. Sarcoma. 2006; 2006(1):91671.
  49. Tran PT, Su Z, Hara W, et al. Long-term survivors using intraoperative radiotherapy for recurrent gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2007; 69(2):504-511.
  50. Vaidya JS, Baum M, Tobias JS, et al. Long-term results of targeted intraoperative radiotherapy (TARGIT) boost during breast-conserving surgery. Int J Radiat Oncol Biol Phys. 2011; 81(4):1091-1097.
  51. Vaidya JS, Joseph DJ, Tobias JS, et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet. 2010; 376(9735):91-102.
  52. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and OS from the TARGIT-a randomised trial. Lancet. 2014; 383(9917):603-613. Erratum in: Lancet. 2014; 383(9917):602.
  53. Valente SA, Tendulkar RD, Cherian S, et al. TARGIT-R (Retrospective): North American experience with intraoperative radiation using low-kilovoltage x-rays for breast cancer. Ann Surg Oncol. 2016; 23(9):2809-2815.
  54. Valentini V, Morganti AG, Macchia G, et al. Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis. Int J Radiat Oncol Biol Phys. 2008; 70(4):1094-1099.
  55. Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013; 14(13):1269-1277.
  56. Willett CG, Czito BG, Tyler DS. Intraoperative radiation therapy. J Clin Oncol. 2007; 25:971-977.
  57. Yoon SS, Chen YL, Kirsch DG, et al. Proton-beam, intensity-modulated, and/or intraoperative electron radiation therapy combined with aggressive anterior surgical resection for retroperitoneal sarcomas. Ann Surg Oncol. 2010; 17(6):1515-1529.
  58. Yu WW, Guo YM, Zhang Q, et al. Benefits from adjuvant intraoperative radiotherapy treatment for gastric cancer: a meta-analysis. Mol Clin Oncol. 2015; 3(1):185-189.
  59. Zeidan YH, Shiue K, Weed D, et al. Intraoperative radiotherapy for parotid cancer: a single-institution experience. Int J Radiat Oncol Biol Phys. 2012; 82(5):1831-1836.
  60. Zeidan YH, Yeh A, Weed D, et al. Intraoperative radiation therapy for advanced cervical metastasis: a single institution experience. Radiat Oncol. 2011; 6:72.
  61. Zur M, Shai A, Leviov M, et al. Short-term complications of intra-operative radiotherapy for early breast cancer. J Surg Oncol. 2016; 113(4):370-373.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Correa C, Harris EE, Leonardi MC, et al. Accelerated partial breast irradiation. Executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol. 2017; 7(2):73-79.
  2. Konski AA, Herman JM, Abdel-Wahab M, et al; Expert Panel on Radiation Oncology–Gastrointestinal. ACR Appropriateness Criteria® recurrent rectal cancer [online publication]. Reston (VA): American College of Radiology (ACR); 2014. Available at: https://acsearch.acr.org/docs/69498/Narrative/ . Accessed on March 14, 2017.
  3. NCCN Clinical Practice Guidelines in Oncology® (NCCN). © 2016-2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on April 28, 2017.
    • Breast Cancer (V2.2017). Revised April 6, 2017.
    • Cervical Cancer (V1.2017). Revised October 10, 2016.
    • Colon Cancer (V2.2017). Revised March 13, 2017.
    • Gastric Cancer (V1.2017). Revised March 21, 2017.
    • Pancreatic Adenocarcinoma (V2.2017). Revised April 27, 2017.
    • Rectal Cancer (V3.2017). Revised March 13, 2017.
    • Soft Tissue Sarcoma (V2.2017). Revised February 8, 2017.
    • Uterine Neoplasm (V1.2017). Revised November 21, 2017.
Websites for Additional Information
  1. American Cancer Society (ACS). External Beam Radiation. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation/science-behind-radiation-therapy/how-is-radiation-given-external-beam-radiation.html . Accessed on March 14, 2017.
  2. National Cancer Institute (NCI). About Cancer. Available at: http://cancer.gov/cancertopics. Accessed on March 14, 2017.
Index

External Beam Intraoperative Radiation Therapy
External Beam Radiation Therapy (EBRT)
Intrabeam Photon Radiosurgery System
IntraOp Mobetron® Intraoperative Electron Radiotherapy
Intraoperative Electron Radiation Therapy (IOERT)
Intraoperative Partial Breast Irradiation (PBI)
Targeted Intraoperative Radiotherapy (TARGIT)

Document History
Status Date Action
 

12/27/2017

The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 01/01/2018 CPT changes; added 19294.
Revised 05/04/2017 Medical Policy & Technology Assessment Committee (MPTAC) review.
Revised 05/03/2017 Hematology/Oncology Subcommittee review. Updated formatting in the Position Statements. Clarified Position Statement for external beam intraoperative radiation therapy as the sole source of additional radiotherapy when criteria are met. Added a MN statement for use of PBI with external beam intraoperative PBI as an alternative to WBI for early-stage breast cancer when criteria are met. Added an INV & NMN statement for external beam intraoperative PBI for breast cancer when the MN criteria are not met. Updated Description, Rationale, Background, Definitions, References, Websites for Additional Information and Index sections.
Reviewed 11/03/2016 MPTAC review.
Reviewed 11/02/2016 Hematology/Oncology Subcommittee review. Updated Rationale, References, Websites for Additional Information, and Index sections.
Reviewed 11/05/2015 MPTAC review.
Reviewed 11/04/2015 Hematology/Oncology Subcommittee review. Revised document # from RAD.00017 to THER-RAD.00004. Updated Rationale, References, and Websites for Additional Information sections. Removed ICD-9 codes from Coding section.
Reviewed 11/13/2014 MPTAC review.
Reviewed 11/12/2014 Hematology/Oncology Subcommittee review. Updated Description, Rationale, Background, References, and Websites for Additional Information sections.
Revised 11/14/2013 MPTAC review.
Revised 11/13/2013 Hematology/Oncology Subcommittee review. Revised Subject (title) of document to External Beam Intraoperative Radiation Therapy. Clarification to the medically necessary statement. Updated Description, Rationale, Background, Definitions, References, Websites for Additional Information, and Index sections.
Reviewed 05/09/2013 MPTAC review.
Reviewed 05/08/2013 Hematology/Oncology Subcommittee review. Updated Rationale, References, Websites for Additional Information, and Index.
Reviewed 05/10/2012 MPTAC review.
Reviewed 05/09/2012 Hematology/Oncology Subcommittee review. Updated Rationale, Definitions, References, and Websites for Additional Information.
  04/01/2012 Updated Coding section with 04/01/2012 HCPCS changes; removed code S8049 deleted 03/31/2012.
  01/01/2012 Updated Coding section with 01/01/2012 CPT changes.
Reviewed 05/19/2011 MPTAC review.
Reviewed 05/18/2011 Hematology/Oncology Subcommittee review. Updated Description, Rationale, References, and Websites for Additional Information.
Revised 05/13/2010 MPTAC review.
Revised 05/12/2010 Hematology/Oncology Subcommittee review. Revised Description and medically necessary Position Statement to clarify and include specific criteria for IORT as boost therapy as follows, adding "at the time of surgical excision" and "when either of the following criteria are met: tumor cannot be completely removed; or tumor has a high risk of recurring in surrounding tissues." Updated Rationale, Coding, and References.
Revised 05/21/2009 MPTAC review.
Revised 05/20/2009 Hematology/Oncology Subcommittee review. Revised medically necessary statement: 1) added "as the sole source of boost therapy" to clarify the use of IORT for specific conditions; 2) added breast cancer as an indication for IORT boost therapy. Revised investigational and not medically necessary statement to include "when criteria are not met, and" for all other indications Updated Rationale, Background, Definitions, Coding, and References.
Revised 11/20/2008 MPTAC review.
Revised 11/19/2008 Hematology/Oncology Subcommittee review. Revised medically necessary statement, added IORT for soft tissue sarcomas and specific examples of pelvic malignancies (e.g. cervical and uterine). Updated Rationale, Coding and References.
Reviewed 11/29/2007 MPTAC review.
Reviewed 11/28/2007 Hematology/Oncology Subcommittee review. Updated Rationale, Background and References. The phrase "investigation/not medically necessary" was clarified to read "investigational and not medically necessary."
  10/01/2007 Updated Coding section with 10/01/2007 ICD-9 changes.
Reviewed 03/08/2007 MPTAC review. Updated Rationale and References.
Reviewed 03/23/2006 MPTAC review. Updated References and added ICD-9 codes.
Revised 04/28/2005

MPTAC review. Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.

Updated coding: Added ICD-9 Diagnoses codes 153-153.98, 157-157.9, 183-183.9

Pre-Merger Organizations

Last Review Date Document Number

Title

Anthem, Inc. 06/16/2003 RAD.00017 Intraoperative Radiation Therapy
WellPoint Health Networks, Inc. 06/24/2004 4.11.01 External Beam Intraoperative Radiation Therapy