Hypofractionation is ‘Excellent Tool’ in Radiotherapy for Lung Cancer

In a conversation with CancerNetwork^® at the 2026 American College of Radiation Oncology (ACRO) Summit, Pranshu Mohindra, MD, spoke about a presentation he gave focusing on the delivery of hypofractionated radiation as a suitable treatment option for patients with lung cancer. He discussed how this modality may offer potential advantages over other strategies such as stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) in select lung cancer populations. He also touched upon considerations for collaborating within multidisciplinary teams to help optimize the use of hypofractionation.

“Physicians and clinical teams should not be afraid of using hypofractionation,” Mohindra stated. “It's an excellent tool to employ in the right settings, and it provides better outcomes for our patients in terms of controlling cancer [and] from the point of logistics, which is a very important aspect for the care that our patients undergo.”

Mohindra is a clinical professor and vice-chair of Operations & Quality in the Department of Radiation Oncology at University Hospitals Cleveland Medical Center/UH Seidman Cancer Center and director of the UH Proton Therapy Center.

CancerNetwork: What was the background for this presentation on the use of hypofractionated radiation for patients with lung cancer?

Mohindra: The whole team at the ACRO Summit is trying to have topics that are of practical relevance. In our field, there is increased use of hypofractionation for a variety of reasons. Lung cancer, which was the topic of my presentation, is also part of that domain where hypofractionation has increasingly become a common practice. At the same time, there is still some education opportunities to develop comfort levels between physician providers to be able to use hypofractionation effectively. The background of this session was to further conversation so [more] providers can start utilizing this for their patients.

What advantages might hypofractionated radiotherapy offer compared with other radiation modalities in lung cancer?

Hypofractionated radiation was truly initiated more for convenience than anything. Historically, radiation treatments have always been very long, protracted courses. That was the necessity because the technology was limited, and the only safe way to do radiation was to do it over a protracted time. As radiation technologies have evolved, we now can deliver higher doses in a daily session, which is the essence for hypofractionation: to give a higher than typical dose. That allows completing the treatment in a shorter timeframe, which has logistic implications. Patients don't have to travel as much for that many weeks for daily radiation treatment, [which] has financial and social implications. It also allows us to better integrate radiation with many systemic treatments, especially for patients who [have] advanced or metastatic disease and unfortunately must go through many rounds of systemic treatments. By doing hypofractionated courses of radiation, we can better interdigitate the radiation in between the chemotherapy, immunotherapy, or systemic therapy cycles, which makes it practical for our referring providers and, most importantly, for our patients, [which] provides a more optimal course.

Are there particular patient factors or circumstances that make hypofractionation more appropriate than others?

In my talk, I tried to split this based on what the stage of the patient is—there are differing approaches of using hypofractionation for early-stage lung cancers vs more locally advanced [disease]—and the scenarios where we are using it for palliation. Broadly speaking, for early-stage lung cancers, we typically will employ hypofractionation when SBRT or SABR is not feasible, most commonly because the tumor is in very close proximity to the airways, the esophagus, the heart, or other mediastinal structures. In those settings where SBRT is not feasible, hypofractionation is a safer way to deliver a high biological dose while reducing the risk of serious bronchovascular or esophageal complications.

In more locally advanced settings, we tend to use it for patients who are not candidates for standard-of-care chemotherapy and radiation delivered concurrently. That could be because of elderly, frail status or other medical comorbidities, or they are refusing chemotherapy for individual reasons. In those settings, hypofractionation allows us to deliver treatments faster and more effectively and be able to continue treatments either sequentially with systemic treatments or look at other supportive care options.

Finally, for palliation, radiation has always been used as a hypofractionated approach with short palliative courses, and that indication remains very valid, especially for inpatients or those who need to be acutely treated and cannot travel. Those are common instances where hypofractionation can be used.

Are there any key clinical data supporting the efficacy of hypofractionated radiation over other modalities or strategies?

Hypofractionated radiation is being compared to standard fractionated radiation, especially in locally advanced settings and with SBRT approaches for early-stage settings. The comparison and the key clinical data have been divided into those 2 domains. For early stage, there are multiple trials which have been reported in the recent few years from US, Canada, and Europe, which have looked at comparing hypofractionated regimens with stereotactic regimens. They have demonstrated superior toxicity profiles, which means a lesser risk of more serious complications with hypofractionated radiation. There are lots of institutional data from large institutions that have reported their experiences by using this approach. Similarly, in the locally advanced setting, the clinical trials have employed hypofractionation, more [often] concurrent with chemotherapy regimens. That continues to be an area for open development of clinical evidence with large randomized phase 3 trials. But evidence for more [patients who are] frail or elderly is typically institutional or limited randomized data.

How can clinicians best manage any toxicities that may emerge with the use of hypofractionation in this lung cancer population?

Toxicity management with hypofractionation will still be per standard of care. Ultimately, it is radiation delivered to the center of the chest or areas around critical structures. The overall management principles stay the same. You still do everything you need to reduce radiation dose to critical organs at risk. There is more emphasis of being mindful of radiation doses to the trachea, the proximal bronchi, the segmental branches of bronchi, the esophagus, and other mediastinal structures when you're using stereotactic or hypofractionated techniques.

Preplanning for those to prevent toxicity is always the best first step. But should a toxicity occur, depending upon where it is, you employ the approach, whether it's pneumonitis management—that's like any other scenario with steroids. If it is airway-related toxicity, that's maybe a little bit more unique with hypofractionation. It then does require partnering with your interventional pulmonology colleagues to look at endoluminal approaches to try to manage those toxicities, whether that's bleeding or stenosis. Similarly, cardiac toxicities [happen] like with any other conventionally fractionated radiation.

What can be done to safeguard a patient's quality of life as they undergo treatment?

One thing that is unique about hypofractionation, and for stereotactic techniques, is during the radiation treatment delivery, more monitoring is required. One aspect that I do cover in my talk is the operational impact of developing a hypofractionated radiation program. For billing requirements and safety reasons, at least in the US, patients who undergo stereotactic radiation do require a physician presence at the treatment consult for direct supervision. For fractionated treatments that are conventionally approached, that requirement is at the day of starting treatment. Then, on a daily basis, it's an offline review. Hypofractionated treatment is somewhere in between, and because these are still high doses with risk of potentially serious toxicities, each department must come up with their workflows to optimize safety for our patients so that these treatments are still being delivered with the highest precision. At the same time, [you must] optimize the involvement with your physics and physician team and your therapy team so that the treatments can be delivered. On the delivery side, that's important to help prevent these complications and maintain patient quality of life.

Downstream, when patients are in the follow-up period, especially if they are on active systemic treatments or have other medical comorbidities that might put them at higher risk, it is equally or even more critically important to follow our patients closely. As radiation oncologists, we are probably in the best position to monitor these toxicities and, as needed, involve our partners—whether that's in medical oncology, interventional pulmonology, or cardiology—to help address or manage toxicities that are more serious in nature.

Looking ahead, where does the field need to go to further optimize the use of hypofractionation and other novel radiotherapy modalities among patients with lung cancer?

For maximizing utilization of hypofractionation, we first need to keep talking about it. In forums like the ACRO Annual Summit, spreading awareness is important in our own practice and health system. We've worked hard to try to get our entire physician team comfortable with the use of hypofractionation. We have set up standard planning guidelines, standard workflows for treatment planning, and peer review so that way we are all supporting each other in the decision-making that goes with hypofractionation.

Finally, on the technology, this is where hypofractionation came into existence because of the modernization of radiation technology. As online adaptive solutions become more prevalent, faster, and efficient, the ideal direction would be, especially for stereotactic and hypofractionated radiations, that all patients undergo daily online adaptive radiation therapy so that we treat on that day based on organs at risk and position. Technologies like protons would also be very helpful in these scenarios. They come with their own unique physical and biological benefits that would allow even stronger benefit in sparing organs at risk, especially with large tumors that are very central or close to critical targets. Evolving technologies will again make hypofractionation more feasible, faster, and safer for our patients.

Overall, what do you hope your colleagues take away from this presentation?

My biggest takeaway from the presentation is to help provide a framework for expanding use of hypofractionation in [providers’] respective clinics. My plan in the presentation was to cover, stepwise, how to approach the treatment planning, the indication, and the decision-making that goes into it. [The presentation] covered the operational workflows for image guidance, and I ended by providing a relatively simplified decision tree that physicians can use in their own respective clinics to help choose various dose regimens that are available for hypofractionation based on whether they are early stage; locally advanced; [receiving] re-radiation, a topic that we didn't discuss much; or in palliative settings.

Reference

Mohindra P. Practical use of hypofractionation in lung cancer. Presented at the 2026 American College of Radiation Oncology Summit; Orlando, FL. February 4-6, 2026.