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Soft Tissue Radionecrosis

Soft Tissue Radionecrosis

Soft Tissue Radionecrosis

INTRODUCTION

Treatment Protocol Guidelines

The following hyperbaric medicine treatment protocol is based upon the recommendations of the Hyperbaric Oxygen Committee of the Undersea and Hyperbaric Medical Society.  Clinical protocols and/or practice guidelines are systematically developed statements that help physicians, other practitioners, case managers and clients make decisions about appropriate health care for specific clinical circumstances.  

Protocols allow health providers to offer evidence-based, appropriate, standardized diagnostic treatment and care services to patients undergoing hyperbaric oxygen therapy (HBOT).  Evidenced-based medicine offers clinicians a way to achieve improved quality, improved patient satisfaction, and reduced costs.  Utilization Review should be initiated when clinical decisions result in deviation from or modification of treatment protocols.  This includes any course of treatment at or above the recognized threshold limits. 

Medical Necessity

Medicare.gov defines “medically necessary” as “health-care services or supplies needed to prevent, diagnose, or treat an illness, injury, condition, disease, or its symptoms and that meet accepted standards of medicine.” 

The following condition meets coverage indications per the National Coverage Determination (NCD) 20.29.[1] Continued HBOT without documented evidence of effectiveness does not meet the Medicare definition of medically necessary treatment. Thorough re-evaluation should be made at least every 30 days for documentation of response to therapy. 

TREATMENT PROTOCOL

(SKIN, PELVIC, BLADDER, RECTUM, COLON, CNS, LARYNX)


BackgroundDelayed (also known as late or chronic) effects of radiation are a complication of modern radiotherapy, which can be treated with HBO. Some examples of delayed radiation effects include soft tissue radionecrosis, radiation cystitis, radiation proctitis, and laryngeal chondroradionecrosis. The basic pathophysiology of delayed radiation tissue damage is endarteritis with resultant tissue hypoxia and secondary fibrosis. 
Goals of HBOT

    • Reduce tissue fibrosis and breakdown by inducing neovascularization and improving tissue oxygenation 
    • Prevent wound dehiscence following soft tissue reconstruction in previously irradiated areas

    Diagnosis

    • Delayed radiation complications are often manifested as non-healing wounds in previously irradiated areas, precipitated by an external insult such as surgery or trauma
    • It is important to differentiate delayed radiation from acute radiation injuries, which usually resolve within a few weeks from radiation exposure and are treated symptomatically.

    Hyperbaric Criteria

    • Non-healing wound on irradiated area with onset at least six months since last radiation exposure  
    • History of radiation treatment (usually in excess of 40 Gray or 4,000 cGy) to the region of the documented injury
    • Wound that is non-responsive to conservative standard treatment 
    • Preparation for definitive wound coverage, with prior failure of coverage attempts 

    Evaluation 

    • Comprehensive history, to include:
      • Date cancer diagnosed
      • Date radionecrosis diagnosed
      • Type, amount, number of treatments and location of radiation
      • Radiation date span
      • Previous treatment or therapies
    • Obtain the radiation-oncology reports  
    • Physical examination
    • Labs to order or review:
      • Complete Blood Count (CBC)
      • Serum Albumin
      • Pre-albumin
      • Erythrocyte Sedimentation Rate (ESR)
      • C-reactive protein (CRP)
    • Wound photographs
    • Chest x-ray
    • Electrocardiogram (ECG)
    • Determine present oncological status
    • Evaluation of tympanic membranes pre and post-treatment as needed
    • Baseline visual acuity assessment
    • smoking/nicotine cessation
    • Nutritional screening

    Treatment

    For cystitis or proctitis
    • 2.0-2.5  ATA oxygen for 90 minutes of oxygen breathing (Table 1 or 3)
    • Daily basis for 20-40 treatments 
    • Referring physician examines the area under direct visualization after 30 treatments and together with the HBO physician decides if to continue to 40. 
    • Further treatments, in 20 treatment increments, will be determined by that examination.
    • Rarely are 60 treatments exceeded. (Requires utilization review)

    For open wounds in an irradiated field

    • 2.0-2.5  ATA oxygen for 90 minutes of oxygen breathing (Table 1 or 3)
    • Daily basis for 20-40 treatments
    • 20 treatments are prescribed prior to any surgical procedure
    • Post-surgical procedure, the patient should receive 10 additional treatments
    • Further treatments, in 20 treatment increments, will be determined by that examination.
    • Rarely are 60 treatments exceeded. (Requires utilization review)
    • Transcutaneous oximetry (TCOM) to determine tissue oxygenation after 20 treatments to indirectly measure increased vascular density
    • After 20 treatments, If measurable signs of healing are present and periwound TCOM values reach 40 mm Hg, HBO may be paused and the wound should be followed for continued healing. 
    •  If measurable signs of healing are present after the initial 20 treatments, re-evaluate if incorrect diagnosis, persistent/recurrent tumor, persistent smoking, or non-responder to HBO. 
    • Wound evaluation and photography weekly and as needed
    • Evaluation of tympanic membranes pre HBO and as needed
    • Smoking Cessation

    Follow-Up

    • Visual acuity assessment for progressive myopia
    • Wound photography
    • TCOM to determine tissue oxygenation

    Treatment Threshold

    20 – 40 treatments; 60 treatments in rare cases. (Utilization review should be requested after 60 treatments)

    Coding


    Refer to the ICD-10 Guideline for the appropriate ICD-10 Code

    Comments

    • If diabetic, blood sugar should be checked 1 hour prior to treatment and post HBO by unit personnel. 
    • Avoid petroleum based dressings and ointments whenever possible. If these are a necessary part of the surgical dressing, ensure that they are not exposed and are completely covered with 100% cotton.

    Primary Sources: Whelan and Kindwall [2], Weaver [3], National Baromedical Services [4]

    DOCUMENTATION

    Radiation doses in excess of 40 Gray (4,000 cGy) are more commonly associated with compromised/delayed healing and persistent soft tissue/ integumentary breakdown within a previously irradiated field that has failed conservative and/or surgical management. The role of hyperbaric oxygen is one of overcoming hypovascular - hypocellular - hypoxic tissue bed and the late-radiation effects. Acute inflammatory responses to ongoing or recently completed radiation therapy need to be differentiated. Relieve the radiotherapy-induced hypoxic/ischemic state by stimulating angiogenesis, thereby overcoming radiation-induced obliterative endarteritis. Below we explain in detail what needs to be documented. See also:

    History and Physical

    • An initial assessment including a history and physical that clearly substantiates the condition for which HBO is recommended.
    • Prior medical, surgical and/or hyperbaric treatments.
    • Past medical records must support history of radiation therapy at the site identified by anatomical location and laterality.

    Physical Exam

    • An initial assessment including a history and physical that clearly substantiates the condition for which HBO is recommended.
    • History of radiation therapy at the site identified by anatomical location and laterality.  Non-responding lesion, within the previously irradiated field.
    • Preparation for definitive coverage, flap or graft.
    • Failure of definitive coverage attempts, flap or graft.
    • Documentation of total radiation dose.
    • Documentation of standard wound care in patients with diabetic wounds.
    • Documentation of optimization of nutritional status.

    Risk Assessment

    • Risk benefit ratio in favor of offering hyperbaric oxygen therapy, example statement:

    The patient was informed of the possible risks and complications of hyperbaric oxygen therapy. These include, but are not limited to, fire, barotrauma of the ears, sinuses, and lungs to include air embolism, central nervous system oxygen toxicity resulting in seizure, cataracts, myopia, and exacerbation of congestive heart failure.

    Having no absolute contraindication to hyperbaric oxygen therapy the patient will be offered treatment at 2.5 ATA for 90 minutes with two inter-current ten minute air breaks (used in the case of mandibular osteoradionecrosis) OR 2.0 ATA for 90 minutes in cases of soft tissue injury. Thirty treatments will initially be provided on a once daily basis Monday through Friday. Thereafter, a re-evaluation of the patient’s clinical progress will be in order to determine if additional treatments may be required.

    Plan

    Example Statement supporting the role of hyperbaric oxygen therapy:

    Mechanisms by which HBO has been shown to be beneficial include the following:

    1. Enhanced fibroblast proliferation – cell proliferation responds to increased tissue levels of oxygen in a dose-dependent fashion.
    2. Collagen maturation – adequate oxygen is provided as a substrate for hydroxylative processes resulting in collagen fibril cross-linking. This collagen scaffolding supports the fragile advancing capillary buds.
    3. Angiogenesis – increased oxygen gradients result in enhanced angiogenesis.

    Sample Order

    CLINICAL EVIDENCE AND RECOMMENDATIONS  

    • 1A
       For patients with refractory radiation proctitis with a history of radiation treatment terminating at least 6 months prior to onset of signs and symptoms, we recommend HBO as an adjunctive therapy to improve healing responses (as demonstrated by SOMA-Lent scores) (Grade 1A)
    • 1B
      For patients who need reconstructive soft tissue surgery or flaps into a previously irradiated area in the head or neck, we recommend HBO therapy to prevent postoperative wound dehiscence (Grade 1B)
    • 2C
      For patients with hemorrhagic radiation cystitis with a history of radiation treatment terminating at least 6 months prior to onset of signs and symptoms, we suggest HBO as an adjunctive therapy to resolve bleeding (Grade 2C) 
    • 2C
      For patients with radio-induced lesions of the larynx with a history of radiation treatment terminating at least 6 months prior to onset of signs and symptoms, we suggest HBO as an adjunctive therapy to promote healing of the radio-induced lesions (Grade 2C). 
      • Rationale: The impact of HBO in terms of its beneficial effects is likely to involve all three of these mechanisms in irradiated tissues: HBO stimulates angiogenesis and secondarily improves tissue oxygenation; reduces fibrosis; and mobilizes and induces an increase of stem cells within irradiated tissues. [5][6] Quality of evidence varies according to the type of irradiated soft tissue being treated. Of note, high-certainty evidence derived from a well-designed randomized clinical trial supports the use of HBO to treat radiation proctitis [7] ; and moderate-certainty evidence supports the use of HBO pre and postoperatively to prevent wound dehiscence following head and neck soft tissue reconstruction in previously irradiated areas [8] . Evidence supporting use of HBO to treat hemorrhagic cystitis and radio-induced lesions of the larynx is of low-certainty, mainly supported by observational studies. [6]
      • Despite benefits, a frequent concern is the fear that HBO will somehow accelerate malignant growth or cause a dormant malignancy to be reactivated. However, an overwhelming majority of both clinical reports and animal studies showed no enhancement of cancer growth. [6] The patient should be informed of the possible risks and complications of hyperbaric oxygen therapy. These include, but are not limited to, fire, barotrauma of the ears, sinuses, and lungs to include air embolism, central nervous system oxygen toxicity resulting in seizure, cataracts, myopia, and exacerbation of congestive heart failure. 
      • Medicare covers preoperative and postoperative use of HBO as an adjunctive therapy for existing soft tissue radionecrosis. Prerequisite for treatment includes history of radiation treatment to the region of the documented injury, terminating at least 6 months prior to onset of signs or symptoms or planned surgical intervention at the site. Numerous forms of soft tissue radiation necrosis and treatment with HBO have been documented with beneficial effect. Tissues previously irradiated with subsequent planned surgery appear to benefit from HBO surrounding the surgery with decreased morbidity from large vessel necrosis. For this reason patients manifesting signs and symptoms of radiation injury will be approved for coincidental HBO, without the histologic diagnosis of ongoing osteoradionecrosis or soft tissue radionecrosis. [9] Utilization review should be accomplished after 60 treatments when HBO is applied to the treatment of radiation injury. Characteristically, most treatment courses for radiation injury will be in the range of 30-60 treatments when the course of treatment is carried out with daily treatments at 2-2.5 ATA of 100% oxygen for 90-120 minutes. [6] 

    CODING

    See ICD-10 Coding for STRN

    APPENDIX

    Summary of Evidence

    We reviewed the guidelines and studies published since guidelines were last updated. Applying the GRADE framework to the combined body of evidence, we found that the use of HBO to:

    • Treat patients with hemorrhagic radiation cystitis is supported by low-certainty evidence (evidence level C) derived from observational studies and case series [6]
    • Prevent postoperative wound dehiscence in patients who undergo soft tissue reconstruction in the head and neck area post irradiation, is supported by moderate-certainty evidence derived from a 2016 Cochrane meta-analysis [8]
    • Treat patients with refractory radiation proctitis (as demonstrated by improvement in SOMA-Lent scores) is supported by high-certainty evidence derived from a large RCT at low risk of bias conducted by Clarke et al.  [7]
    • Treat patients with radio-induced lesions of the larynx is supported by low-certainty evidence derived from observational studies and case series  [6]

    Systematic reviews:     

    • A 2016 systematic review [10] included 8 studies (1 uncontrolled observational cohort, 5 case series, and 2 case reports) including 720 participants who received HBOT for radiation induced skin necrosis.  [11] [12] [13] [14] [15] [16] [17] [18] Sites of skin necrosis included lower extremity, buttocks , scrotum, abdomen, chest wall, upper extremity, and head and neck. Majority of studies were at high risk of bias. Six studies provided the primary outcome measure of interest: complete wound healing after HBOT (98 patients). Pooled together the rate of complete wound healing was 79.6% (78/98). Two studies provided the secondary outcome measures of interest, symptomatic improvement of skin necrosis after HBOT (622 patients). Pooled together the rate of symptomatic improvement was 86% (535/622). Further analysis revealed the rate of complete resolution of pain symptoms was 30% (187/6 22), wound healing symptoms 30% (187/622), and wound drainage symptoms 39%(243/ 622). Evidence level is considered as low certainty (evidence level C) as currently no randomized control trial has tested the efficacy of HBOT in the treatment of skin necrosis due to late radiation tissue injury. Authors concluded that HBO is a safe intervention with promising outcomes, however additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation induced skin necrosis. 
    • A 2016 Cochrane systematic review [8] included 14 trials (753 participants) that assessed the effect of HBO on complete mucosal cover in people with osteoradionecrosis and on wound healing of dehiscence following complex head and neck surgery and irradiation. 2 RCTs (264 participants) assessed soft tissue radiation injuries and showed that HBO is effective in promoting healing of dehiscence following complex head and neck surgery and irradiation (moderate quality evidence, RR 4.23 95% CI, (1.06 to 16.83) of from single studies there was a significantly increased chance of improvement or cure following HBO for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5). Authors concluded that these small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome.

    Guidelines:

    • The 2014 UHMS HBO Therapy Indications Book (Guidelines) and the 2017 European Committee for Hyperbaric Medicine Guidelines support the use of HBOT as therapy to treat Soft Tissue Radiation Necrosis, and although the guidelines use different evidence grading methodologies, they are in agreement regarding strength of recommendation.  [6]  [19] See table below:

    HBO therapy for Soft Tissue Injury

    UHMS, 2014

    ECHMG, 2017

    Treatment of soft tissue injury

    AHA Level Ib 

    n/a

    Treatment of hemorrhagic radiation cystitis 

    n/a

    Grade 1B

    Treatment of radiation proctitis

    n/a

    Grade 1A

    The treatment of soft-tissue radionecrosis (other than cystitis and proctitis), in particular in the head and neck area

    n/a

    Grade 2C

    Treating or preventing radio-induced lesions of the larynx 

    n/a

    Grade 3C

    Randomized Clinical Trials                       

    • In 2008, Clarke et al conducted an RCT with 120 evaluated participants that compared the effects of HBO on the late effects normal tissue-subjective, objective, management, analytic (SOMA-LENT) score and standardized clinical assessment in patients with chronic refractory radiation proctitis [7]. In the experimental group, the mean was lower (p = 0.0150) and the amount of improvement nearly twice as great (5.00 vs. 2.61, p = 0.0019). Similarly, Group 1 had a greater portion of responders per clinical assessment than did Group 2 (88.9% vs. 62.5%, respectively; p = 0.0009). Significance improved when the data were analyzed from an intention to treat perspective (p = 0.0006). Authors concluded that hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis, generating an absolute risk reduction of 32% (number needed to treat of 3) between the groups after the initial allocation. The study is considered by the 2016 Cochrane systematic review [8] as at low risk of bias (evidence level A). 

    Observational Studies

    • Case series support use of HBO to resolve hemorrhagic radiation cystitis  [6] (level C)
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    REFERENCES

    1. CMS. National Coverage Determination (NCD) for Hyperbaric Oxygen Therapy (20.29) . Date of publication 2017;.
    2. Harry T. Whelan, Eric Kindwall et al. Hyperbaric Medicine Practice 4th Edition Best Publishing Company. Date of publication 2017;volume fourth():.
    3. Weaver L . "Hyperbaric Oxygen Therapy Indications” Best Publishing Company, North Palm Beach, FL . Date of publication 2014;volume 469(13th Edition,):.
    4. National Baromedical Services. Introduction to Hyperbaric Medicine Primary Training Manual .;.
    5. Feldmeier JJ. Hyperbaric oxygen therapy and delayed radiation injuries (soft tissue and bony necrosis): 2012 update. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... Date of publication 2012;volume 39(6):1121-39.
    6. Undersea and Hyperbaric Medical Society Hyperbaric Oxygen Committee,, et al. Hyperbaric Oxygen Therapy Indications . Date of publication 2014;.
    7. Clarke RE, Tenorio LM, Hussey JR, Toklu AS, Cone DL, Hinojosa JG, Desai SP, Dominguez Parra L, Rodrigues SD, Long RJ, Walker MB et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. International journal of radiation oncology, biology, physics. Date of publication 2008;volume 72(1):134-143.
    8. Bennett MH, Feldmeier J, Hampson NB, Smee R, Milross C et al. Hyperbaric oxygen therapy for late radiation tissue injury. The Cochrane database of systematic reviews. Date of publication 2016;volume 4():CD005005.
    9. Novitas Solutions, Inc et al. Local Coverage Determination for Hyperbaric Oxygen (HBO) Therapy (L35021) . Date of publication 2015;.
    10. Borab Z, Mirmanesh MD, Gantz M, Cusano A, Pu LL et al. Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. Date of publication 2017;volume 70(4):529-538.
    11. Bui QC, Lieber M, Withers HR, Corson K, van Rijnsoever M, Elsaleh H et al. The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects. International journal of radiation oncology, biology, physics. Date of publication 2004;volume 60(3):871-8.
    12. Feldmeier JJ, Heimbach RD, Davolt DA, Court WS, Stegmann BJ, Sheffield PJ et al. Hyperbaric oxygen as an adjunctive treatment for delayed radiation injury of the chest wall: a retrospective review of twenty-three cases. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... Date of publication 1995;volume 22(4):383-93.
    13. Feldmeier JJ, Heimbach RD, Davolt DA, Court WS, Stegmann BJ, Sheffield PJ et al. Hyperbaric oxygen an adjunctive treatment for delayed radiation injuries of the abdomen and pelvis. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... Date of publication 1996;volume 23(4):205-13.
    14. Feldmeier JJ, Heimbach RD, Davolt DA, McDonough MJ, Stegmann BJ, Sheffield PJ et al. Hyperbaric oxygen in the treatment of delayed radiation injuries of the extremities. Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, In.... Date of publication 2000;volume 27(1):15-9.
    15. Hampson NB, Holm JR, Wreford-Brown CE, Feldmeier J et al. Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen for chronic radiation tissue injury. Cancer. Date of publication 2012;volume 118(15):3860-8.
    16. Korpinar S, Cimsit M, Cimsit B, Bugra D, Buyukbabani N et al. Adjunctive hyperbaric oxygen therapy in radiation-induced non-healing wound. The Journal of dermatology. Date of publication 2006;volume 33(7):496-7.
    17. Niezgoda JA, Serena TE, Carter MJ et al. Outcomes of Radiation Injuries Using Hyperbaric Oxygen Therapy: An Observational Cohort Study. Advances in skin & wound care. Date of publication 2016;volume 29(1):12-19.
    18. Uzun G, Candas F, Mutluoglu M, Ay H et al. Successful treatment of soft tissue radionecrosis injury with hyperbaric oxygen therapy. BMJ case reports. Date of publication 2013;volume 2013():.
    19. Mathieu, Daniel; Marroni, Alessandro; Kot, Jacek et al. Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving and hyperbaric medicine. Date of publication 2017;volume 47(1):24-32.
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