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How Radiation for Lung Cancer Can Lead To Pulmonary Hypertension

Posted on October 26, 2022
Medically reviewed by
Steven C. Pugliese, M.D.
Article written by
Andrew J. Funk, DC, DACNB

Radiation therapy is a cancer treatment that uses high levels of energy aimed at specific areas of the body to kill cancer cells and shrink tumors. Cancer doctors often prescribe radiation therapy combined with other cancer treatments like chemotherapy and surgery.

The lungs are a common site for radiation therapy, as many types of cancer start in or near the lungs or even spread to the lungs from another location (metastasis). Unfortunately, despite its cancer-reducing benefits, radiation treatment can lead to long-term effects in the lungs. For example, pulmonary hypertension (PH) may occur after radiation therapy for lung cancer. PH is a condition when the pressure in the blood vessels inside the lungs gets too high, putting strain on the heart, and possibly leading to heart failure.

Common Types of Cancer Affecting the Lungs

Cancers affecting the lungs are divided into the following categories:

  • Primary lung cancer — Cancer that began in the lungs
  • Mediastinal cancer — Cancer of the mediastinum, which is the part of the chest that sits between the lungs
  • Secondary lung cancer, or metastasis — Cancer that began elsewhere, then spread to the lungs

Primary Lung Cancers

Primary lung cancer is divided into two major groups:

  • Small cell lung cancer (SCLC) — 15 percent to 20 percent of all lung cancers
  • Non-small cell lung cancer (NSCLC) — 80 percent to 85 percent of all lung cancers

The three main kinds of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Radiation therapy is commonly used to treat both small cell and non-small cell lung cancers.

Mediastinal Cancers

The mediastinum sits just behind the chest bone (sternum), in front of the spine, and between the left and right lungs. The mediastinum includes the:

  • Heart — Organ that pumps blood to the lungs to get oxygen, then pumps the blood around the body
  • Aorta — Wide blood vessel that carries blood from the heart to the body
  • Thymus — Immune system organ that helps protect the body from infection
  • Esophagus — Food pipe
  • Trachea — Windpipe
  • Lymph nodes — Part of the immune system

The mediastinum is divided into the anterior, middle, and posterior parts. Oncology providers do not use radiation therapy for every type of mediastinal cancer. The most common kinds of mediastinal cancers that require radiation are:

  • Anterior mediastinum — Thymic cancer, lymphoma, and germ cell tumors
  • Middle mediastinum — Most common cancers of this region do not normally receive radiation therapy.
  • Posterior mediastinum — Neurogenic tumor

Secondary Lung Cancers

Many types of cancer begin in one part of the body and move to the lungs. This happens when the rapidly dividing cancer cells spread to neighboring body tissues or get into the blood or lymph vessels and spread to more distant parts of the body — becoming what is called a malignancy.

Here are the most common kinds of cancer that spread to the lungs and often require radiation therapy:

  • Breast cancer
  • Colon cancer
  • Rectal cancer
  • Head and neck cancers
  • Kidney cancer
  • Uterine cancer
  • Lymphoma

How Radiation Injury Is a Risk Factor for Pulmonary Hypertension

Radiation therapy is a powerful cancer treatment, but it may cause lung injury and disease. This happens in four phases, usually over weeks to months:

  • Cell injury — Radiation toxicity causes DNA damage or mutations, injuring the lung cells, leading to apoptosis (cell death).
  • Inflammatory response — Inflammatory cells release chemicals to prepare for healing.
  • Repair process — Special immune cells called macrophages release growth factors (chemicals) that repair damage and promote the healing of cells and blood vessels (called tissue and vascular remodeling). This begins the slow process of fibrosis (scarring) of tissues and blood vessels.
  • Further injury — During the inflammatory and repair phases, swelling and lack of oxygen occur, causing further blood vessel damage. This can cause more cell injury, and the cycle starts again.

Because of this cycle, a person may develop radiation pneumonitis within two to four months after radiation. Symptoms of radiation pneumonitis include mild to severe dyspnea (shortness of breath) and a cough that produces no mucus or blood.

In addition, scarring or fibrosis can continue to slowly build over time, causing conditions called radiation fibrosis or interstitial lung disease. This typically happens months to years after radiation therapy.

A study by the American Cancer Society found that of 12,390 childhood cancer survivors, 3.5 percent who underwent radiation therapy of the chest had developed pulmonary fibrosis 20 years after their diagnosis.

Pulmonary Hypertension After Radiation

Radiation fibrosis can eventually lead to PH. The vessels that move blood in the lungs become scarred, raising the blood pressure within them. Additionally, scarring can prevent the lung tissues from expanding properly.

The World Health Organization (WHO) divides PH into categories (or classes) based on what caused the condition. When PH develops as a result of radiation damage, it is classified as group 3 PH, or PH due to lung disease.

St. Jude Hospital studied a group of adults who had survived childhood cancer. They found that 25 percent of the adults who underwent chest radiation treatment as children had abnormally high pressure readings in the lungs when measured by echocardiogram, indicating possible PH. There are no studies in adults to know how common PH is after developing radiation fibrosis.

Diagnosis and Prognosis of PH From Lung Radiation

PH caused by lung fibrosis from radiation often leads to symptoms, including:

  • Shortness of breath
  • Tiredness
  • Dizziness
  • Swelling in the legs or feet
  • Chest pain
  • A racing or pounding heart

Those with a history of chest radiation therapy should tell their doctor if they begin noticing symptoms of PH, even years or decades after radiation treatment. Left untreated, PH can lead to heart disease and even heart failure. However, it’s important to remember that PH is rare and that these symptoms are much more often caused by other less serious conditions.

Diagnosis of PH is usually carried out with an echocardiogram. This test creates an ultrasound picture of the heart and measures pressure in the pulmonary artery using sound waves. If PH is a possibility based on this test, doctors typically perform right heart catheterization. During this procedure, a thin tube is placed into the blood vessels of the lungs and the blood pressure is measured.

There are no large studies looking at how well people recover from PH if they developed it after radiation treatment. However, detecting PH symptoms early and starting treatment as soon as possible are key to increasing the chances of the best possible outcome.

Treatments for PH Due to Radiation

When PH is caused by another condition such as lung disease, it’s often managed by treating the underlying factor. Unfortunately, this is difficult to do for PH caused by lung fibrosis. Although some medications can treat early lung damage and radiation pneumonitis, most treatments won’t work on long-term scarring and fibrosis due to radiation.

Very early research has found that a couple of medications may reduce radiation-induced fibrosis — nintedanib (Ofev) and pirfenidone (Esbriet). However, clinical trials are needed before it’s clear whether these treatments are effective.

There hasn’t been much research into understanding how to treat radiation-induced PH, so doctors don’t yet know which therapies are most likely to work.

Doctors may recommend PH treatments that boost the heart’s ability to pump blood, prevent blood clots, or improve PH symptoms.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 48,000 members come together to ask questions, give advice, and share their stories.

Are you living with pulmonary hypertension? Have you undergone radiation therapy? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Radiation Therapy To Treat Cancer — National Cancer Institute
  2. Lung Irradiation Induces Pulmonary Vascular Remodelling Resembling Pulmonary Arterial Hypertension — Thorax
  3. Lung Metastases — American Cancer Society
  4. Types of Lung Cancer — Cancer Research UK
  5. Mediastinal Tumor — Cleveland Clinic
  6. Mediastinal Cancer — StatPearls
  7. Malignancy — National Cancer Institute
  8. Secondary Breast Cancer in the Lung — Breast Cancer Now
  9. Curative Radiotherapy Using Different Radiation Techniques for Isolated Lung Metastasis From Colorectal Cancer — Tumori
  10. Role of Radiotherapy in the Treatment of Metastatic Head and Neck Cancer — OncoTargets and Therapy
  11. Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases From Renal Cell Carcinoma — A Multicenter Analysis of the German Working Group "Stereotactic Radiotherapy" — Journal of Thoracic Disease
  12. Radiation Therapy for Uterine Cervical Cancer With Lung Metastases Including Oligometastases — In Vivo
  13. Radiation Therapy for Lung for Malignant Lymphoma — Oncolex Oncology Encyclopedia
  14. Pulmonary Complications of Childhood Cancer Treatment — Paediatric Respiratory Reviews
  15. Pulmonary Hypertension Secondary to Pulmonary Fibrosis: Clinical Data, Histopathology, and Molecular Insights — Respiratory Research
  16. Pulmonary Complications in Survivors of Childhood and Adolescent Cancer — American Cancer Society
  17. Pulmonary Hypertension as a Complication of Pediatric Cancer — Global Pediatric Health
  18. Pulmonary Hypertension — Mayo Clinic

All updates must be accompanied by text or a picture.
Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Andrew J. Funk, DC, DACNB has held board certification in neurology with the American Chiropractic Neurology Board since 2015. Learn more about him here.

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