5-Fraction Preoperative SBRT in Pancreatic Cancer: Quality of Life and Survival?
In this article
Are 5 fractions possible instead of 28?
Patients preparing for pancreatic cancer surgery often approach this major operation after months of chemotherapy, tired and weakened. Some centers also give these patients preoperative radiotherapy; the conventional approach, alongside chemotherapy, takes 28 fractions over 5-6 weeks to complete. Presented at the American Society for Radiation Oncology (ASTRO) meeting in September 2026, the SOFT Preop trial investigated whether this could instead be replaced by just 5 fractions of stereotactic body radiotherapy (SBRT) before surgery. The result: Patients receiving SBRT were in better physical condition and experienced less fatigue before surgery; the rate of residual cancer in lymph nodes was similar in both groups. However, the survival figures require careful interpretation.
- Study: 102 patients with pancreatic cancer who had received chemotherapy were randomly assigned before surgery to 5-fraction SBRT or 28-fraction chemoradiotherapy (phase 2, single center).
- Primary objective: The rate of residual cancer in lymph nodes at surgery was 41% with SBRT and 38% with chemoradiotherapy; the difference was not significant. Surgical complications and surgical margins were also similar.
- Quality of life: Before surgery, physical function was better and fatigue lower in the SBRT group. The difference disappeared after surgery.
- Caution: Median survival was 26 months with SBRT and 43 months with chemoradiotherapy; survival at 3 years was 43% versus 58%. The difference was not statistically significant, but the study was not designed with sufficient power to compare survival.
- Conclusion: A promising quality-of-life advantage, but larger studies are needed before concluding that SBRT can replace chemoradiotherapy.
First, the background: why preoperative treatment in pancreatic cancer?
Pancreatic cancer is among the most difficult cancers to treat. In the United States, 5-year survival is still only around 13%. Surgery is the only chance of cure, but only a small proportion of patients are operable at diagnosis. Depending on the tumor's relationship with the surrounding major vessels, the disease is classified as resectable, borderline resectable (borderline) or locally advanced disease. For general information on disease stages and treatment options, see our pancreatic cancer guide for an overview.
In recent years, particularly in borderline resectable disease, administering chemotherapy before surgery (usually FOLFIRINOX) has become standard. This approach aims both to shrink the tumor and to treat spread invisible to the eye early. The role of adding radiotherapy to chemotherapy remains controversial.
Figure 1 · The treatment pathway in pancreatic cancer
The treatment plan is determined by the tumor's relationship with surrounding vessels.
How was the SOFT Preop trial conducted?
The trial led by Prof. William Hall at the Medical College of Wisconsin in the United States (NCT03704662) enrolled 102 patients from 2018 onward with resectable, borderline resectable or selected locally advanced pancreatic cancer. All patients had tolerated at least 1 month of chemotherapy, most had received chemotherapy for more than 2 months, and none had definite evidence of distant spread. Patients were randomly assigned to two groups:
- SBRT group: Radiation in 5 fractions: 25-35 Gy to the tumor and 25 Gy to at-risk lymph node regions. No concurrent chemotherapy was given.
- Chemoradiotherapy group: 50,4 Gy of radiation in 28 fractions with concurrent chemotherapy.
In both groups, at-risk lymph node regions were treated along with the tumor, and surgery was planned for 4-6 weeks after radiotherapy. The study's primary objective was the proportion of patients with residual cancer in lymph nodes removed at surgery.
Figure 2 · How was SOFT Preop designed?
Two different radiotherapy schedules after chemotherapy, followed by surgery.
Main findings
| Outcome | SBRT (5 fractions) | Chemoradiotherapy (28 fractions) |
|---|---|---|
| Residual cancer in lymph nodes (primary objective) | %41 | %38 |
| Tumor response, complications, surgical margins | similar | similar |
| Preoperative physical function and fatigue | better | worse |
| Locoregional recurrence (patient count) | 6 | 2 |
| Median progression-free survival | ~14 months | ~22 months |
| Median survival (from study entry) | 26 months | 43 months |
| Median survival (those completing all treatment) | 39,6 months | 45,5 months |
| Alive at 3 years | %43 | %58 |
Source: ASTRO 2026 press release (LBA 08) and ASCO Post. Median follow-up approximately 3,4 years. None of the differences in recurrence or survival was statistically significant; hazard ratios and p values were not disclosed.
Quality of life: the clearest difference
The clearest difference between the two methods was seen in patients' self-reported quality of life before surgery. Patients receiving SBRT reported significantly better physical function and overall physical health than those receiving chemoradiotherapy, and experienced less fatigue during this period. According to Prof. Hall, this difference was concentrated precisely during radiotherapy: One group completed treatment in 5 visits, while the other came to the hospital every day for weeks. After surgery, the difference between groups disappeared. The press release did not specify which questionnaire measured quality of life or the magnitude of the difference.
How should these results be interpreted?
- The survival difference should not be ignored. Median survival was 26 months in the SBRT group and 43 months in the chemoradiotherapy group; survival at 3 years was 43% versus 58%. This means approximately 15 fewer people alive at 3 years per 100 patients. The difference was not statistically significant, but the study was not large enough to detect it. “No significant difference” and “no difference” are not the same.
- Recurrence and disease progression point in the same direction. Locoregional recurrence occurred in 6 patients with SBRT and 2 with chemoradiotherapy; median progression-free survival was 14 versus 22 months.
- Single center, phase 2. The study was conducted at a single center by a team experienced in pancreatic cancer. Whether the results can be replicated at other centers is unknown.
- Equivalence was not demonstrated. The investigators explicitly state that the study was not designed to show that the two methods are equivalent in cancer control.
- A distinctive SBRT schedule. The SBRT in this study treats lymph node regions along with the tumor, at a lower dose. Because it differs from other SBRT approaches that target only the tumor, the results cannot be generalized to them.
- Selected patients. Only patients who had tolerated chemotherapy and shown no distant spread were enrolled; moreover, survival was calculated from study entry rather than the start of chemotherapy. Consequently, survival in both groups appears better than in the general population of patients with pancreatic cancer.
- Still only a conference presentation. Hazard ratios, p values and details of the quality-of-life scales will be available in the peer-reviewed article.
Figure 3 · The two sides of the scale
Findings favoring SBRT and findings requiring caution.
What do other studies say?
The role of preoperative radiotherapy in pancreatic cancer remains unclear despite several important studies in recent years:
| Study | Comparison | Result |
|---|---|---|
| PREOPANC (Netherlands, 2022) | Preoperative gemcitabine + radiotherapy versus immediate surgery | Alive at 5 years: 20,5% versus 6,5%. Favors preoperative treatment. |
| PREOPANC-2 (Netherlands, 2025) | Preoperative FOLFIRINOX versus gemcitabine + radiotherapy | Median survival 21,9 and 21,3 months; no difference. |
| Alliance A021501 (United States, 2022) | FOLFIRINOX versus FOLFIRINOX + short-course radiotherapy (including SBRT) in borderline resectable disease | The radiotherapy arm was closed early; survival at 18 months was 66,7% versus 47,3%, disfavoring radiotherapy. |
| CONKO-007 (Germany, 2025) | Chemotherapy versus chemotherapy + chemoradiotherapy in locally advanced disease | A higher rate of clear surgical margins among those undergoing surgery; no survival difference. |
| SOFT Preop (United States, 2026) | 5-fraction SBRT versus 28-fraction chemoradiotherapy after chemotherapy | Similar pathological outcomes; quality of life favors SBRT; survival numerically favors chemoradiotherapy. |
The Alliance A021501 trial is particularly important in this table: Outcomes were also worse in the arm with added short-course radiotherapy (SBRT or 5-fraction hypofractionated radiotherapy). The survival trend in SOFT Preop does not remove this question mark. Conversely, PREOPANC-2 showed similar outcomes with chemoradiotherapy and intensive chemotherapy. We discussed treatment options after preoperative FOLFIRINOX in this article, and the importance of a complete response to preoperative treatment in our article on pathological complete response previously.
What do guidelines recommend?
- ASTRO (August 2026 update): Preoperative radiotherapy or chemoradiotherapy is recommended in borderline resectable disease to improve locoregional control and the rate of clear surgical margins; preoperative chemoradiotherapy is conditionally recommended in resectable disease; SBRT is considered appropriate for selected patients with locally advanced disease.
- NCCN: Preoperative treatment is recommended in borderline resectable disease; chemoradiotherapy or SBRT after chemotherapy is an option “in selected patients.”
- ESMO (2023): Recommends preoperative FOLFIRINOX or gemcitabine–nab-paclitaxel in borderline resectable disease; chemoradiotherapy should be considered “case by case.”
As shown, the radiation oncology guideline gives radiotherapy a broader role, while medical oncology guidelines are more cautious. This difference indicates that the decision should be individualized in a multidisciplinary tumor board. We described approaches combining chemotherapy, radiotherapy and surgery in locally advanced pancreatic cancer in a separate article previously.
- A common and serious cancer: According to the International Agency for Research on Cancer's (IARC) 2024 estimates, approximately 6.100 people are diagnosed with pancreatic cancer each year in Türkiye and approximately 5.800 die from it. Pancreatic cancer ranks 11. in incidence and 4. in cancer-related deaths.
- The technology is available: Many centers in Türkiye have radiotherapy equipment capable of SBRT. However, pancreatic cancer SBRT requires experience because of its proximity to moving organs; it should be remembered that this study was also conducted by an experienced team.
- The center making the decision matters: Pancreatic cancer operations are recommended at centers that perform a high volume of pancreatic surgery each year and where surgeons, oncologists, radiation oncologists, radiologists and gastroenterologists work together.
Practical information for patients
- Learn how your disease is classified. Whether it is resectable, borderline or locally advanced determines the treatment plan.
- Ask for a tumor board assessment. Whether to give preoperative radiotherapy and which schedule to use should be a joint decision by the surgeon, oncologist and radiation oncologist.
- Ask about the options. If radiotherapy is recommended, discuss the advantages and disadvantages of 5-fraction and 28-fraction options, the center's experience and the limits of the evidence.
- Value quality of life, but do not make it the sole criterion. Shorter treatment makes everyday life easier; however, questions about cancer control must also be considered.
- Try to enter surgery in a strong condition. Pay attention to nutrition during chemotherapy and radiotherapy and stay as active as your strength allows; this facilitates recovery after surgery.
- Ask about clinical trials. Many questions in this field are still being investigated; a suitable clinical trial may be a good option.
Frequently asked questions
- Should everyone receive radiotherapy before pancreatic cancer surgery?
- No. The role of preoperative radiotherapy is controversial, and guidelines differ. It is generally considered after chemotherapy in selected patients with borderline resectable disease. The decision should be made by a multidisciplinary tumor board.
- Is 5-fraction SBRT as effective as 28-fraction treatment?
- In this study, pathological outcomes at surgery were similar. However, survival and recurrence figures numerically favored chemoradiotherapy, and the study was not large enough to answer this question. It is therefore still too early to say “equally effective.”
- What is SBRT's advantage?
- Treatment is completed in approximately 1-2 weeks and 5 visits instead of 5-6 weeks, and no concurrent chemotherapy is required. In this study, patients receiving SBRT were in better physical condition and experienced less fatigue before surgery.
- Do these results also apply to patients with locally advanced, inoperable disease?
- Only selected patients with locally advanced disease were enrolled, and all patients were followed according to a treatment plan aimed at surgery. Higher-dose SBRT approaches are being investigated separately in patients with inoperable disease. Other developments in this field are covered in our article on advances in pancreatic cancer treatment for further reading.
- I have been offered SBRT; should I accept it?
- SBRT is an established option used at experienced centers. However, when making this decision, it is appropriate to ask the team recommending treatment why they chose this schedule, about their center's experience and about the limits of the evidence. If possible, ensure that the decision is made by a tumor board.
Glossary
- SBRT
- Stereotactic body radiotherapy. A radiotherapy method that delivers a high dose in a small number of fractions with millimeter precision.
- Chemoradiotherapy
- Radiotherapy given together with chemotherapy during the same period to enhance its effect.
- Borderline resectable pancreatic cancer
- A situation in which the tumor has limited contact with the surrounding major vessels, making surgery possible but clear margins difficult to achieve.
- Neoadjuvant treatment
- Chemotherapy, radiotherapy or both given before surgery.
- Pathological response
- Assessment of how much preoperative treatment affected the tumor by examining the surgically removed tissue under a microscope.
- Progression-free survival
- The period after treatment during which the disease does not progress.
- Phase 2 trial
- A study investigating initial signals of a treatment's efficacy and safety, generally requiring confirmation in larger phase 3 trials for definitive conclusions.
DROZDOGAN Academy Commentary
For a patient with pancreatic cancer, every week of treatment is valuable; going to and from the hospital every day after months of chemotherapy is no small burden. SOFT Preop shows that reducing this burden may be possible. But the main goal in pancreatic cancer is both to help the patient feel better and to help them live longer.
⚡ Why it matters
Reducing preoperative radiotherapy from 28 to 5 fractions preserves quality of life in tired patients and may help them approach surgery in a stronger condition. Demonstrating in a randomized trial that this did not worsen pathological outcomes is important.
✅ Strengths
Randomized design; a fair comparison with lymph node regions treated in both arms; patient-reported quality-of-life data; approximately 3,4 years of follow-up.
⚠️ Limitations
Single center, 102 patients, phase 2. Survival and recurrence figures numerically disfavor SBRT, and the difference is not small (approximately 15 people per 100 patients at 3 years). The short-course radiotherapy arm also had worse outcomes in Alliance A021501. Hazard ratios and details of the quality-of-life scales have not yet been disclosed.
🩺 What to do in practice
- Make the decision on preoperative radiotherapy in a tumor board discussion.
- In patients scheduled for radiotherapy, consider 5-fraction SBRT as an option, at experienced centers and with an explicit discussion of the limits of the evidence.
- Explain to the patient both the quality-of-life advantage and the uncertainty about survival together.
- If possible, refer patients to clinical trials for participation.
❓ Open questions
Is the survival difference in SOFT Preop real, or a chance result of a small sample? Can multicenter phase 3 trials demonstrate the same quality-of-life advantage without compromising cancer control? What will the role of preoperative radiotherapy be in the era of more effective drug treatments?
Is this a first? To our knowledge, this is the first randomized study comparing 5-fraction preoperative SBRT with 28-fraction chemoradiotherapy in pancreatic cancer.
Our brief judgment: SBRT better preserves patients' quality of life before surgery and does not worsen surgical outcomes. However, the unfavorable trend in survival and recurrence figures indicates that it is still too early to say this approach can replace standard chemoradiotherapy. A promising beginning, rather than the final word.
- This article was prepared in September 2026 using the ASTRO 2026 press release (copies from Newswise and News-Medical), the ASCO Post report, the ClinicalTrials.gov record (NCT03704662), the study's 2023 design article, abstracts of PREOPANC, PREOPANC-2, Alliance A021501 and CONKO-007 publications, ASTRO 2019 and 2026, NCCN and ESMO guidelines, and American Cancer Society and IARC data.
- Reported from secondary sources: SOFT Preop results were reported only from the press release and news reports; the full article has not yet been published. SBRT doses were taken from the study design article and registry information. Findings from the other studies were reported from journal abstracts and news sources. Recommendation levels in the ASTRO 2026 update were taken from the press release.
- Not verified: The SBRT dose actually delivered to patients, the concurrent drug used in chemoradiotherapy, the quality-of-life scale and magnitude of the difference, p values and hazard ratios, surgery rates and clear surgical margin rates by group; the type of preoperative chemotherapy patients received; the wording in the most recent NCCN version; the prevalence of pancreatic SBRT in Türkiye.
- Based on general knowledge: The simplified explanation of pancreatic cancer classification, the approximately 5-6-week duration of 28-fraction treatment, the experience required for pancreatic SBRT and the recommendation to perform pancreatic surgery at high-volume centers are presented as established knowledge.
- The absolute difference calculation (approximately 15 people per 100 patients at 3 years), evidence table, diagrams and Academy commentary are our own. The diagrams were derived from verified statements in the text; they contain no new data.
- This article is not personal medical advice.
Sources
- Hall WA et al. A randomized, phase II clinical trial of SBRT or conventionally fractionated concurrent chemotherapy and radiation therapy preoperatively for pancreatic adenocarcinoma: the SOFT Preop study. ASTRO 2026 Annual Meeting, Abstract LBA 08.
- American Society for Radiation Oncology. Short-course radiation therapy better preserves physical function before pancreatic cancer surgery. Press release, 28 September 2026.
- The ASCO Post. Short-course SBRT better preserves physical function before pancreatic cancer surgery. 29 September 2026.
- Saif A et al. SOFT Preop study design. Ann Surg Oncol. 2023;30(2):688-690.
- ClinicalTrials.gov. NCT03704662.
- Versteijne E et al. Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the PREOPANC trial. J Clin Oncol. 2022;40(11):1220-1230.
- PREOPANC-2: neoadjuvant FOLFIRINOX versus gemcitabine-based chemoradiotherapy. Lancet Oncol. 2025.
- Katz MHG et al. Efficacy of preoperative mFOLFIRINOX vs mFOLFIRINOX plus hypofractionated radiotherapy for borderline resectable pancreatic adenocarcinoma (Alliance A021501). JAMA Oncol. 2022.
- Fietkau R et al. CONKO-007. J Clin Oncol. 2025;43:3266-3278.
- American Society for Radiation Oncology. Radiation therapy for pancreatic cancer: clinical practice guideline update. Pract Radiat Oncol. 2026.
- National Comprehensive Cancer Network. Pancreatic adenocarcinoma guidelines.
- Conroy T et al. Pancreatic cancer: ESMO clinical practice guideline. Ann Oncol. 2023.
- American Cancer Society. Cancer Statistics, 2026.
- IARC Global Cancer Observatory. Türkiye fact sheet, 2024.
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