Subject:
Radiation Therapy for Esophageal Cancer
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Over the past several decades, methods to plan and deliver radiation therapy have evolved in ways that permit more precise targeting of tumors with complex geometries. Earlier methods involved two-dimensional treatment planning based on flat images, and radiation beams with cross-sections of uniform intensity that were sequentially aimed at the tumor along 2 or 3 intersecting axes. These methods were collectively termed conventional external beam radiation therapy (EBRT).
Subsequent enhancement evolved using 3-dimensional images, usually from computed tomography (CT) scans, to delineate the tumor, its boundaries with adjacent normal tissue, and organs at risk for radiation damage. Radiation oncologists used these images, displayed from a "beam's-eye-view", to shape each of several beams (e.g., with compensators, blocks, or wedges) to conform to the patient's tumor geometry perpendicular to the beam's axis. Computer algorithms were developed to estimate cumulative radiation dose delivered to each volume of interest by summing the contribution from each shaped beam. Methods also were developed to position the patient and the radiation portal reproducibly for each fraction, and immobilize the patient, thus maintaining consistent beam axes across treatment sessions. However, "forward" planning used a trial and error process to select treatment parameters (the number of beams and the intensity, shape, and incident axis of each beam). The planner/radiotherapist modified one or more parameters and recalculated dose distributions, if analysis predicted underdosing for part of the tumor or overdosing of nearby normal tissue. Furthermore, since beams had uniform cross-sectional intensity wherever they bypassed shaping devices, it was difficult to match certain geometries (e.g., concave surfaces). Collectively, these methods are termed 3-dimensional conformal radiation therapy (3D-CRT).
Other methods were subsequently developed to permit beam delivery with non-uniform cross-sectional intensity. This often relies on a device (multi-leaf collimator, MLC) situated between the beam source and patient that moves along an arc around the patient. As it moves, a computer varies aperture size independently and continuously for each leaf. Thus, MLCs divide beams into narrow "beamlets", with intensities that range from zero to 100% of the incident beam. Beams may remain on as MLCs move around the patient (dynamic MLC), or they may be off during movement and turned on once the MLC reaches prespecified positions ("step and shoot" technique). Another method of delivering radiation beam uses a small radiation portal emitting a single narrow beam that moves spirally around the patient, with intensity varying as it moved. This method, also known as tomotherapy or helical tomotherapy, is described as the use of a linear accelerator inside a large "donut" that spirals around the body while the patient laid on the table during treatment. Each method (MLC-based or tomotherapy) is coupled to a computer algorithm for "inverse" treatment planning. The planner/radiotherapist delineates the target on each slice of a CT scan, and specifies that target's prescribed radiation dose, acceptable limits of dose heterogeneity within the target volume, adjacent normal tissue volumes to avoid, and acceptable dose limits within the normal tissues. Based on these parameters and a digitally-reconstructed radiographic image of the tumor and surrounding tissues and organs at risk, computer software optimizes the location and shape of beam ports, and beam and beamlet intensities, to achieve the treatment plan's goals. Collectively, these methods are termed intensity-modulated radiation therapy (IMRT).
According to ECRI Institute, there are two different approaches to image-guided radiation therapy that are in current use: pre-treatment imaging and real-time guidance. IMRT is an example of a method that uses pre-treatment imaging to prepare a treatment plan. In contrast, real-time guidance utilizes real-time imaging (at the time of treatment) to guide treatment. It provides real-time, online images of the radiation target area from a computed tomography (CT) scanner before, during, and after therapy. Patient positioning, radiation field alignment, and collimator positioning can be verified and adjusted before and during irradiation. This approach should, in theory, provide more accurate radiation delivery than conventional IMRT. Organ motion, day-to-day variations in tumor position, and differences in patient positioning in each treatment session could be taken into account with real-time imaging.
Policy:
(NOTE: This policy only applies to adult members. It does not apply to pediatric members.
For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
I. Neoadjuvant treatment
A. For an individual with stage T1b node-positive or T2-T4a disease, the use of 23 to 28 fractions of three-dimensional conformal radiation therapy (3DCRT) is considered medically necessary.
II. Adjuvant treatment (if no preoperative or prior irradiation given)
A. For an individual with squamous cell carcinoma when there are positive margins or adenocarcinoma with at least pT2 or node-positive disease, the use of 25 to 28 fractions of 3DCRT is considered medically necessary.
III. Definitive treatment
A. For an individual with T1b node-positive or T2-T4a disease, the use of 25 to 28 fractions of 3DCRT is considered medically necessary.
B. For tumors located in the cervical esophagus, up to 39 fractions of 3DCRT or IMRT is considered medically necessary.
IV. Palliation
A. The use of 15 fractions of 3DCRT is considered medically necessary.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for three-dimensional conformal radiation therapy (3DCRT). Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy for Radiation Therapy for Esophageal Cancer.
Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has issued a determination for Intensity-Modulated Radiation Therapy (IMRT). Per LCD L36711 and Local Coverage Article: Billing and Coding: Intensity Modulated Radiation Therapy (IMRT) (A56725), IMRT is covered for limited indications when LCD L36711 and A56725 criteria is met. For additional information and eligibility, refer to Local Coverage Determination (LCD): Intensity Modulated Radiation Therapy (IMRT) (L36711) and Local Coverage Article: Billing and Coding: Intensity Modulated Radiation Therapy (IMRT) (A56725). Available at: https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=36711&ver=18&name=314*1&UpdatePeriod=749&bc=AAAAEAAAAAAAAA%3d%3d&.
[INFORMATIONAL NOTE:
I. Neoadjuvant chemoradiotherapy (CRT)
Historically, surgery alone has been associated with relatively high rates of recurrence and dismal rates of survival. Among the treatments investigated to improve upon these results is the use of preoperative chemoradiotherapy.
One of the largest randomized controlled trials to investigate preoperative CRT was the CROSS trial. In this trial, 368 patients with resectable clinical stage T1N1 or T2-3N0-1M0 squamous cell carcinoma, adenocarcinoma or large-cell undifferentiated carcinoma of the esophagus and gastroesophageal junction (GEJ) were randomized to preoperative CRT (carbo/taxol with 41.4 Gy) followed by surgery or to surgery alone. At a median follow up of 45.4 months, the median overall survival (OS) was 24.0 months (CRT) vs. 4.94 months (surgery alone). The OS at 1, 2, 3, and 5 years was 82% vs. 70%, 67% vs. 50%, 58% vs. 44% and 47% vs. 34%, respectively for preoperative CRT vs. surgery alone. Other benefits to preoperative CRT included a significantly higher R0 resection (92% vs. 69%), higher incidence of a pathological complete response (pCR) (29% vs. 23%), a lower incidence of node positivity (31% vs. 75%) and no difference in occurrence of postoperative complications.
A recent analysis of CROSS I and II trials revealed a reduced rate of local-regional recurrence (LRR) with preoperative CRT (34.7% vs. 57.1%). Furthermore, the majority of these recurrences had a component of distant recurrence whereas the rate of an isolated LRR was (3.3% vs. 9.3%).
Finally, a large meta-analysis revealed a significant reduction in all-cause mortality with preoperative CRT (hazard ratio [HR] 0.78) compared with surgery alone, translating into an absolute survival benefit of 8.7% at 2 years (Sjoquist et al., 2011).
II. Adjuvant chemoradiotherapy (CRT)
A. Squamous cell carcinoma
There is no definitive evidence of a benefit with postoperative CRT. For example, a randomized control trial of 45 patients found no significant improvement with postoperative CRT vs. postoperative chemotherapy (Tachibana et al., 2003). It is also noted that NCCN recommends adjuvant treatment only in the setting of a R1 or R2 resection.
B. Adenocarcinoma
Postoperative CRT is indicated for an individual with stage IB-IV (M0) based on the INT 0116 study. In INT 0116, 559 patients with stage IB-IV adenocarcinoma of the stomach or GEJ (20% of patients) following R0 resection were randomized to CRT (5-FU/leucovorin before, during and concurrent with radiation to 45 Gy) or to no further treatment. In the most recent update with a 10-year median follow up, CRT continues to show a significant improvement in OS (HR 1.32) and for relapse-free survival (RFS) (HR 1.51). This benefit extended to all T stages, N stages as well as location in the GEJ.
III. Definitive chemoradiotherapy (CRT)
In an individual who is not medically operable or who refuses surgery, definitive CRT remains the standard treatment. This is primarily based on data from RTOG 8501 (Herskovic et al., 1992). In this randomized stratified phase III trial, patients with T1-3, N0-1, M0 squamous cell carcinoma or adenocarcinoma (90% were squamous cell carcinoma) of the esophagus, including GEJ, were randomized to radiation alone (to 64 Gy) or CRT (50 Gy + 5-FU/cisplatin). In the most recent update, 5-year survival was 0% vs. 26% and persistence of disease was 37% vs. 25% favoring the CRT arm for both measures (Cooper et al., 1999).
In an attempt to improve upon these results, INT 0123 evaluated radiation dose escalation in combination with chemotherapy (Minsky et al., 2002). Two hundred and thirty-six (236) patients with T1-4, N0-1 squamous cell carcinoma or adenocarcinoma were randomized to 50.4 Gy + 5-FU/cisplatin or 64.8 Gy + 5-FU/cisplatin. It is noted "…because of the concern that the stomach could not safely tolerate 64.8 Gy, eligibility was limited to patients whose tumors did not extend to within 2 cm of the GEJ." This trial was stopped early due to an increase in death in the high-dose arm.
Specifically, 11 deaths occurred in the high-dose arm vs. 2 in the standard-dose arm. Of these 11 deaths, 7 occurred at or below a dose of 50.4 Gy. As such, the standard-dose arm was associated with a non-significant improvement in median survival (18.1 months vs. 13 months) and 2-year survival (40% vs. 31%). On the other hand, the high-dose arm was associated with a non-significant reduction in local-regional persistence or failure (50% vs. 55%) and in distant failure (9% vs. 16%). As a result of these findings, the authors conclude, "…the standard radiation dose is 50.4 Gy."
In a quality of life (QOL) analysis (Kachnic et al., 2011), the high-dose arm had a significantly lower total QOL at the end of CRT (p = 0.02). At 8 and 12 months, the high-dose arm had a lower total QOL as compared to the standard arm, though this was not statistically significant. These results support that the high-dose arm does not improve patient QOL. The authors state, "…these results lend further weight to our previous conclusion that radiotherapy to 50.4 Gy should remain the standard of care in patients treated with definitive CRT for esophageal cancer."
IV. Treatment technique
Recently published data from RTOG 0617 suggests that, on multivariate analysis cardiac volume (V), V5 and V30 predict patient survival. Though there is no indication that similar findings will be borne out of INT 0123, it underscores the importance of cardiac dose. For example, in the treatment of esophageal carcinoma, several studies have confirmed an association between cardiac dose and toxicity.
Konski et al. (2012) found that symptomatic cardiac toxicity correlated with the whole heart V20, V30 and V40. Symptomatic toxicity was not observed if the whole heart V20, V30 and V40 was kept below 70%, 65% or 60%, respectively. In addition, Tait et al. (2013) also found a correlation of cardiac V20, V30 and V40 with toxicity whereby patients with a V20 above 71%, a V30 above 64.5% and V40 above 57% had increased odds of developing cardiac toxicity.
In attempt to reduce dose to nearby critical structures, several studies have evaluated the use of IMRT.
For example, Kole et al. (2012) revealed that in the treatment of 19 patients with carcinoma of the distal esophagus, IMRT significantly reduced heart dose, spared more of right coronary artery and improved target conformity.
Using a fitted multivariate inverse probability weighted-adjusted Cox model, Lin et al. (2012) found that patients treated with 3DCRT had significantly greater risk of dying (72.6% vs. 52.9%) and of local regional recurrence. In addition, and increased cumulative incidence of cardiac death was also seen.
IMRT should be considered with caution, however, due to the integral dose within the lungs. For example, Kumar et al. (2012) found that IMRT, compared to 3DCRT, increased the lung V20 and that a V20 of > 15% increased the risk of chronic pneumonitis.
Other studies have also shown the effect of low-dose radiation within the lung. For example, Gergel et al.(2002) found that, in the 3D treatment of esophageal cancer in 20 patients, the percent of absolute lung volume that received a total dose between 7 and 10 Gy may be significantly correlated with the percent decline of carbon monoxide diffusing capacity, total lung capacity and vital capacity.
Lee et al. (2003) also found an increase in postoperative pulmonary complications when the pulmonary V10 was greater than 40% and when the V15 was greater than 30%. In an update of this study, Wang et al. (2006) revealed that the pulmonary V5 correlated with postoperative pulmonary complications.
NCCN GuidelinesTM indicate that IMRT “…is appropriate in clinical settings where reduction in dose to organs at risk (e.g., heart, lungs) is required that cannot be achieved by 3-D techniques.” Given this and the available data, the use of IMRT will be considered on a case-by-case basis.]
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Radiation Therapy for Esophageal Cancer
Radiation Treatment of Carcinoma of Esophagus and Gastroesophageal Junction (GEJ) Cancer
Esophagus Cancer, Radiation Therapy
Gastroesophageal Junction (GEJ) Cancer, Radiation Therapy
Cancer of Esophagus and Gastroesophageal Junction (GEJ), Radiation Therapy
References:
1. Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomized, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb; 16(2):187-199.
2. Cooper JS, Guo MD, Herskovic A, et al. Chemoradiotherapy of locally advanced esophageal cancer. Long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999 May 5; 281(17):1623-1627.
3. Gergel TJ, Leichman L, Nava HR, et al. Effect of concurrent radiation therapy and chemotherapy on pulmonary function in patients with esophageal cancer: dose-volume histogram analysis. Cancer J. 2002 Nov-Dec; 8(6):451-460.
4. Herskovic A, Martz K, Al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11; 326(24):1593-1598.
5. Kachnic LA, Winter K, Wasserman T, et al. Longitudinal quality-of-life analysis of RTOG 94-05 (Int 0123): A phase III trial of definitive chemoradiotherapy for esophageal cancer. Gastrointest Cancer Res. 2011 Mar-Apr; 4(2):45-52
6. Kole TP, Aghayere O, Kwah J, et al. Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for distal esophageal cancer. Int J Radiation Oncol Biol Phys. 2012 Aug 1; 83(5):1580-1586.
7. Konski A, Li T, Christensen M, et al. Symptomatic cardiac toxicity is predicted by dosimetric and patient factors rather than changes in 18F-FDG PET determination of myocardial activity after chemoradiotherapy for esophageal cancer. Radiotherapy and Oncology. 2012 Jul; 104(1):72-77.
8. Kumar G, Rawat S, Puri A, et al. Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation or IMRT. Jpn J Radiol. 2012; 30(1):18-24
9. Lee HK, Vaporciyan AA, Cox JD, et al. Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters. Int J Radiation Oncol Biol Phys. 2003 Dec 1; 57(5):1317-1322.
10. Lin SH, Wang L, Myles B, et al. Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs. intensity-modulated radiotherapy for esophageal cancer. Int J Radiation Oncol Biol Phys. 2012 Dec 1; 84(5):1078-1085.
11. MacDonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6; 345(10):725-730.
12. Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: High-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1; 20(5):1167-1174.
13. National Comprehensive Cancer Network (NCCN) Guidelines® Version 4.2019 - December 20, 2019. Esophageal and Esophagogastric Junction Cancers. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers. 4.2019. ©2019 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN®. To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org.
14. Oppendijk V, van der Gaast A, van Lanschot JJB, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol. 2014 Feb 10; 32(5):385-391.
15. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011 Jul; 12(7):681-692.
16. Smalley SR, Benedetti JK, Haller DG, et al. Updated analysis of SWOG-directed Intergroup Study 0116: A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1; 30(19):2327-2333.
17. Tachibana M, Yoshimura H, Kinugasa S, et al. Postoperative chemotherapy vs. chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial. EJSO. 2003 Sep; 29(7):580-587.
18. Tait LM, Meyer JE, McSpadden E, et al. Women at increased risk for cardiac toxicity following chemoradiation therapy for esophageal carcinoma. Practical Radiation Oncology. 2013 Oct-Dec; 3(4):e149-155.
19. van Hagen P, Hulshof MCCM, van Lanschot JJB, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31; 366(22):2074-2084.
20. Wang S, Liao Z, Vaporciyan A, et al. Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. Int J Radiation Oncol Biol Phys. 2006 Mar 1; 64(3):692-699.
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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