Chemoradiation for Lung Cancer: Why Chemotherapy and Radiation Work Better Together. For some people with lung cancer—particularly stage III non-small cell lung cancer (NSCLC)—chemotherapy and radiation therapy may work better when they are given together than when they are given separately.
If you are just learning about lung cancer, start here.
This approach is called concurrent chemoradiation or concurrent chemoradiotherapy (CRT).
The concept is relatively straightforward:
Radiation attacks cancer in the chest, while chemotherapy can both attack cancer systemically and make cancer cells more sensitive to radiation.
The tradeoff is equally important.
Giving chemotherapy and radiation together can increase treatment toxicity, particularly:
- Esophagitis and difficulty swallowing
- Fatigue
- Nausea
- Low blood counts
- Weight loss
- Lung inflammation
- Infection risk
For patients healthy enough to tolerate the combination, however, research has demonstrated a survival advantage compared with giving chemotherapy and radiation sequentially.
And lung cancer treatment has changed considerably since I originally wrote this article.
Today, many patients with unresectable stage III NSCLC who complete chemoradiation without disease progression may subsequently receive durvalumab (Imfinzi) immunotherapy.
That development has significantly changed the outlook for this group of lung cancer patients.
I am a long-term survivor of an incurable blood cancer called multiple myeloma.
Though I have been in complete remission from my blood cancer since 1999, I have developed long-term side effects that cause joint, muscle, nerve, and bone pain. I spend as much time and money managing my therapy-induced pain as I do managing my health. I hope the post below helps you manage your own cancer pain. My point is that managing cancer is about BOTH length of life and quality of life. Please consider the complementary therapies discussed below to help manage possible side effects.
Like most topics on PeopleBeatingCancer.org, I believe that patient education is the key to managing a problem.
Scroll down and post a question or comment if there is anything you’d like to know about cancer and pain.
Good luck,
David Emerson
Concepts Central to Managing Your Cancer
Lung Cancer Therapies:
What Is Chemoradiation?
Chemoradiation combines two established cancer treatments.
- Chemotherapy travels throughout the body and can attack cancer cells both within and outside the primary tumor.
- Radiation therapy delivers concentrated energy to the tumor and surrounding areas at risk for cancer involvement.
When chemotherapy is given at the same time as radiation, certain chemotherapy drugs can act as radiosensitizers, making cancer cells more vulnerable to radiation damage.
This is one reason the combination may produce better local cancer control than either treatment alone.
Patients should understand, however, that there are two different approaches:
Concurrent chemoradiation
Chemotherapy and radiation are administered during the same treatment period.
Sequential chemoradiation
Chemotherapy and radiation are given one after the other.
That distinction matters.
Research comparing the two approaches has generally found better long-term survival with concurrent chemoradiation, although concurrent treatment also causes more acute toxicity.
A meta-analysis of randomized trials involving more than 2,600 patients found that concurrent chemoradiotherapy improved 2-, 3-, 4- and 5-year survival compared with sequential therapy and reduced the risk of local-regional recurrence.
The downside was an increased risk of serious side effects, particularly esophagitis, nausea/vomiting and suppression of blood counts.
Research:
Concurrent vs. Sequential Chemoradiotherapy for Patients With Advanced Non-Small-Cell Lung Cancer
Read the study on PubMed
An earlier randomized phase III trial also demonstrated a long-term survival advantage for concurrent treatment. Five-year survival was 16% with one concurrent regimen versus 10% with sequential therapy, although severe acute esophagitis occurred considerably more often with concurrent treatment.
Research:
Sequential vs. Concurrent Chemoradiation for Stage III NSCLC — RTOG 9410
Read the full study
Who May Benefit From Chemoradiation?
One of the most important points for patients is that chemoradiation is not appropriate for every person with lung cancer.
The strongest evidence applies to selected patients with locally advanced stage III NSCLC, particularly when the cancer cannot be removed surgically but remains confined enough to be treated with definitive radiation.
Factors that may influence whether concurrent treatment is appropriate include:
- Stage of the cancer
- Tumor location
- Lymph-node involvement
- Lung function
- Performance status
- Age and frailty
- Heart disease
- Kidney function
- Nutritional status
- Ability to tolerate chemotherapy
- Previous cancer treatments
Patients who are not able to tolerate concurrent therapy may sometimes receive chemotherapy and radiation sequentially.
This is an important distinction because the goal should not simply be to prescribe the most aggressive therapy possible.
The goal is to identify the treatment strategy that offers the best balance between cancer control, survival and treatment toxicity for the individual patient.
The Major Change: Immunotherapy After Chemoradiation
This is probably the most important update to the original version of this article.
Chemoradiation is no longer necessarily the end of treatment for unresectable stage III NSCLC.
The landmark PACIFIC trial studied patients whose cancer had not progressed after platinum-based concurrent chemoradiation.
Patients were randomized to receive either the immune checkpoint inhibitor durvalumab or placebo.
Long-term follow-up demonstrated:
| Outcome |
Durvalumab |
Placebo |
| Median overall survival |
47.5 months |
29.1 months |
| 5-year overall survival |
42.9% |
33.4% |
| Median progression-free survival |
16.9 months |
5.6 months |
| 5-year progression-free survival |
33.1% |
19.0% |
These results helped establish consolidation durvalumab following chemoradiation as a standard treatment approach for appropriate patients with unresectable stage III NSCLC.
Research:
Five-Year Survival Outcomes From the PACIFIC Trial
Read the full PACIFIC study
The National Cancer Institute also discusses the evidence supporting durvalumab following concurrent chemoradiation in its comprehensive NSCLC treatment overview.
NCI — Non-Small Cell Lung Cancer Treatment
Chemoradiation Can Be Effective—but It Can Also Be Difficult
There is an important lesson here that sometimes gets lost when discussing survival statistics.
More effective treatment can also mean more treatment toxicity.
Concurrent chemotherapy and chest radiation can produce overlapping side effects.
Esophagitis
Radiation can inflame the esophagus.
Patients may develop:
- Painful swallowing
- Difficulty swallowing
- Heartburn-like discomfort
- Reduced food intake
- Weight loss
- Dehydration
Severe esophagitis can occasionally interrupt treatment.
Both chemotherapy and radiation can cause fatigue.
When the treatments are combined, fatigue can become substantial and may continue for weeks after treatment ends.
Chemotherapy can suppress bone marrow function, leading to:
- Anemia
- Neutropenia
- Thrombocytopenia
This can increase fatigue, infection risk, and bleeding risk.
Radiation Pneumonitis
Radiation to the chest can cause inflammation of healthy lung tissue.
Symptoms can include:
- Dry cough
- Shortness of breath
- Chest discomfort
- Fatigue
- Fever
Radiation pneumonitis generally develops weeks or months after radiation rather than immediately.
For a broader discussion of radiation therapy and its potential benefits and risks, see:
Radiation for Lung Cancer: What Patients Need to Know
Chemotherapy Matters Too
Chemotherapy regimens used with radiation commonly contain platinum chemotherapy.
Depending on the patient’s cancer and overall health, regimens may include combinations such as:
- Cisplatin + etoposide
- Carboplatin + paclitaxel
- Cisplatin + pemetrexed for selected nonsquamous cancers
- Cisplatin + vinorelbine
The appropriate regimen depends on tumor histology, kidney function, hearing, neuropathy risk, performance status, and other factors.
PeopleBeatingCancer discusses systemic treatment in greater detail here:
Chemotherapy for Lung Cancer: What Patients Need to Know
One question I encourage patients to ask is:
“Why are you recommending this particular chemotherapy regimen with my radiation, and what alternatives could provide similar cancer control with less toxicity?”
Long-Term Side Effects Matter
One of my concerns as a long-term cancer survivor is that cancer treatment discussions often focus heavily on getting through therapy.
But survival is only part of the story.
Patients who live years after treatment may experience late effects.
Chest radiation and chemotherapy can potentially contribute to:
- Pulmonary fibrosis
- Persistent shortness of breath
- Chronic fatigue
- Peripheral neuropathy
- Cardiovascular disease
- Reduced exercise capacity
- Chronic pain
- Difficulty swallowing
- Reduced quality of life
This doesn’t mean patients should avoid potentially curative therapy.
It means patients should understand both sides of the equation:
What might this treatment do for my cancer—and what might this treatment do to me?
For patients experiencing cancer- or treatment-related discomfort, see:
Lung Cancer and Pain: What Patients and Survivors Need to Know
Can Patients Reduce the Side Effects of Chemoradiation?
There is no supplement, diet or complementary therapy that can substitute for potentially curative chemoradiation in an appropriate stage III lung cancer patient.
But supportive and integrative care may help patients maintain strength and manage some treatment-related symptoms.
Areas worth discussing with your oncology team include:
Maintaining calories and protein can become difficult when radiation causes esophagitis.
Patients losing weight should consider asking for an oncology dietitian before significant weight loss occurs.
Appropriately scaled physical activity may help preserve strength, function and quality of life.
For some patients, even short daily walks or supervised rehabilitation can be useful.
For patients who smoke, stopping remains one of the most important steps they can take during and after lung cancer treatment.
Exercise, nutrition, and functional preparation before intensive cancer therapy may help selected patients enter treatment with greater physiologic reserve.
Symptom management
Don’t wait until a side effect becomes severe.
Report:
- Increasing shortness of breath
- New cough
- Fever
- Painful swallowing
- Difficulty eating
- Rapid weight loss
- Dehydration
- Severe fatigue
- New numbness or tingling
early.
Some side effects are much easier to manage when treatment begins promptly.
Questions to Ask Your Oncologist
If chemoradiation has been recommended, I would consider asking:
- What stage and type of lung cancer do I have?
- Is the goal of treatment cure, long-term control, or symptom relief?
- Why are you recommending concurrent rather than sequential chemoradiation?
- What chemotherapy drugs will I receive?
- What radiation dose and technique will be used?
- How much healthy lung and heart tissue will receive radiation?
- What is my personal risk of radiation pneumonitis?
- How likely am I to develop significant esophagitis?
- What should I do if eating or swallowing becomes difficult?
- Should I meet with an oncology dietitian or rehabilitation specialist before treatment begins?
- If my cancer does not progress after chemoradiation, am I a candidate for durvalumab?
- Should my case be reviewed by a multidisciplinary lung cancer team?
That last question may be particularly important.
Stage III lung cancer can involve decisions among medical oncology, radiation oncology, thoracic surgery, pulmonology, and other specialties.
PeopleBeatingCancer Evidence Rating
Concurrent Chemoradiation for Appropriate Stage III NSCLC
Evidence Rating: 🟢 Strong
Randomized trials, meta-analyses, and clinical guidelines support concurrent platinum-based chemotherapy plus radiation for appropriately selected patients with unresectable stage III NSCLC.
Concurrent treatment provides better long-term cancer control and survival than sequential treatment for many fit patients, but it also increases acute toxicity.
Durvalumab After Chemoradiation
Evidence Rating: 🟢 Strong
For appropriate patients with unresectable stage III NSCLC whose cancer has not progressed following concurrent chemoradiation, randomized clinical-trial evidence demonstrates substantial improvements in progression-free and overall survival with consolidation durvalumab.
At five years in the PACIFIC trial, approximately 42.9% of patients receiving durvalumab were alive, compared with 33.4% receiving placebo.
The Bottom Line
The original research that prompted me to write this article made an important point:
Chemotherapy and radiation can work synergistically against lung cancer.
That conclusion has held up.
But our understanding of the treatment has advanced considerably.
For appropriately selected patients with unresectable stage III NSCLC, concurrent chemoradiation generally provides better long-term outcomes than giving chemotherapy and radiation sequentially, although the combined treatment can produce more side effects.
And today the story doesn’t necessarily end when chemoradiation ends.
For appropriate patients whose cancer has not progressed, consolidation immunotherapy with durvalumab can further improve long-term survival.
The challenge for patients is therefore not simply deciding whether chemotherapy or radiation “works.”
The more useful questions are:
What combination of therapies gives me the best chance of controlling my cancer?
What are the short- and long-term risks?
And what can I do before, during and after treatment to maintain my health and quality of life?
Those are the questions I believe every lung cancer patient deserves clear answers to.
Chemoradiation for Lung Cancer Chemoradiation for Lung Cancer Chemoradiation for Lung Cancer
