Sarcomas are among the rarest forms of cancer – and that rarity is precisely what makes them so challenging. These malignant tumors can develop in soft tissue or bone and may occur anywhere in the body. In Germany, approximately 2,500 to 3,200 people are diagnosed with a sarcoma each year, accounting for around 1% of all new cancer cases. Despite their rarity, this tumor group comprises more than 100 different subtypes that vary greatly in behavior, growth patterns, and treatment approaches. Early diagnosis and treatment at specialized centers are therefore crucial for prognosis.
The editorial team of the Leading Medicine Guide had the opportunity to speak with Professor Tonus, a specialist at the Sarcoma Center in Hamburg, where she offers intraoperative radiation therapy and is considered one of the leading experts in this field.
The location of a sarcoma often shapes the surgical strategy more strongly than any other characteristic of the tumor – sometimes even more than its size or biological behavior. If a sarcoma is located in close proximity to nerves, major blood vessels, or sensitive organs, the entire surgical planning process changes, because oncological radicality and preservation of function must be carefully balanced.
“The diagnosis is so challenging because sarcomas are a true rare disease – a condition that occurs extremely infrequently. The incidence is only about three to five cases per 100,000 people. If you calculate using an average of four per 100,000 and apply that proportion to a population of around 80 million, you arrive at approximately 2,500 to 3,200 new cases per year. Depending on which incidence rate and population figure are used, the number of annual cases in Germany falls somewhere between 3,000 and 4,000. We are therefore dealing with something that is not only rare but additionally complicated by its enormous diversity – more than 200 different types are now known. This number continues to rise because diagnostic methods are becoming increasingly precise. With refined immunohistochemical staining and ever more sophisticated detection techniques, more variants can be identified. The more precisely we search, the more distinct forms we find. This exact equation – rare disease, increasingly precise diagnostics, and therefore a rapid rise in identified subtypes – means that even specialized centers encounter many of these rare entities only a few times each year,” Professor Tonus explains at the beginning of our conversation.
Specialized sarcoma centers are essential to consolidate expertise and achieve sufficiently high case volumes. Only in this way can the necessary diagnostic and therapeutic quality be ensured.
“The patients who arrive at these centers have often followed very different paths. Many – especially younger people – are digitally savvy, conduct research early on, read hospital reviews, and specifically seek out specialized institutions. Some already come with findings and a suspicion of sarcoma before any biopsy has even been performed. Even the biopsy itself must meet strict quality criteria, such as fan biopsies with at least six, preferably more, tissue samples. Others are referred or follow recommendations. And then there is the opposite extreme: people who present only at a very advanced, metastatic stage, searching for a last hope – even though treatment at that point often offers no realistic benefit anymore,” Prof. Dr. Tonus notes.
Experience shows that tumors measuring approximately five centimeters or more may begin to undergo malignant transformation – a finding based on large cohort studies conducted in England.
Prof. Dr. Tonus illustrates the surgical approach: “To explain this, I like to use a simple image: A benign lipoma can be removed like a ball, clearly demarcated and without the need for a major safety margin. A sarcoma, on the other hand, is operated on in such a way that I never actually see the tumor itself. It remains completely surrounded by a healthy tissue envelope that is removed along with it. Everything directly bordering the tumor must also be resected. That is the principle of sarcoma surgery: the good sarcoma surgeon never sees the tumor. If a tumor lies directly adjacent to major vessels or nerves, these structures may need to be replaced, reconstructed, or – depending on the extent of the defect – sacrificed. The spectrum ranges from small tumors to retroperitoneal masses weighing up to 20 kilograms. Surgical complexity therefore always depends on the location. If a tumor is favorably situated, for example in the groin region surrounded by muscle tissue and away from critical vessels or nerves, it can often be removed without collateral damage. However, when large tumors wrap around major arteries, veins, or nerves, surgery becomes much more difficult. In the leg, for example, this may involve the femoral nerve in the front or the sciatic nerve in the back. While the limb itself may be preserved, its function may be lost. In such cases, one must carefully weigh whether surgery is appropriate or whether targeted radiation – such as stereotactic therapy – may represent an alternative.”
Once the diagnosis of a medium-sized sarcoma has been established, there is no acute medical emergency requiring surgery on the same day. Nevertheless, prompt action is necessary – but only after the guideline-based diagnostic workup has been fully completed.
“The process begins with imaging: someone notices a newly developed swelling, or an MRI has already been performed. This is followed by a biopsy in the form of a fan biopsy, during which multiple samples are taken from suspicious areas. These are sent to the pathologist, and if malignancy is confirmed, staging with CT scans of the thorax and abdomen follows, because sarcomas typically metastasize to the lungs. Only then is the case discussed in the multidisciplinary tumor board. In very large tumors, neoadjuvant therapy may be beneficial. A so-called ‘Sarculator’ helps estimate the risk of recurrence or death; if this exceeds 60 percent, pre-treatment is recommended. Despite the urgency, confirmation of a malignant tumor does not mean that one should suddenly shift into sprint mode. What matters is a rapid but structured approach in accordance with the guidelines,” Prof. Dr. Tonus emphasizes regarding the treatment process.
Intraoperative radiation therapy (IORT) can offer a significant therapeutic advantage in selected situations because it addresses the limitations of conventional radiation techniques. It is applied directly during surgery after tumor removal and allows highly precise irradiation of the tumor bed before the body is closed again. This creates possibilities that cannot be achieved with external radiation therapy alone.
Prof. Dr. Tonus explains the benefits of IORT in detail: “In the retroperitoneum, sarcomas can become extremely large before they are clinically noticeable at all – the abdominal cavity compensates for a long time, and many patients simply notice that they need to loosen their belts more and more. Such tumors must be operated on regardless of size. Yet even after removal, achieving a wide safety margin is not always possible. Often, only a very narrow layer of healthy tissue remains, and sometimes merely microscopic residual disease – an R1 situation. This is exactly where the flap comes into play. Once inserted after tumor removal, it allows precise modeling of the tumor bed. This enables radiation to be directed exactly to the area where the tumor was located. The advantage is obvious: localization is optimal because the surgeon is directly on site and already operating. No additional opening of the abdomen is necessary; everything takes place in a single procedure. Furthermore, radiation-sensitive structures can deliberately be spared. The small intestine or ureters can be positioned outside the radiation field, and the corresponding segments of the radiation applicators are left unloaded. This planning is performed together with physicists and radiation oncologists and is individually adapted to the patient’s anatomy.”
Intraoperative radiation therapy is a procedure associated with very few complications, which plays an important role in patient counseling. Many patients also find it reassuring that part of the required radiation dose can already be delivered during surgery.
Regarding this, Prof. Dr. Tonus explains: “If, for example, a total postoperative dose of 50 Gy is required and an intraoperative boost of around 15 Gy can be applied, the remaining dose – and therefore the number of subsequent radiation sessions – is reduced. Three aspects are crucial: targeted placement directly at the tumor bed, the low complication rate, and the ability to keep radiation-sensitive organs out of the field using retractors. The flap, as shown in the images, allows highly precise coverage of the target area. Radiation dose calculation follows a clear principle. What matters is whether the tumor has been completely removed or whether microscopic residual disease may remain that cannot be seen with the naked eye. Such residual disease usually extends only a few millimeters deep. That is precisely why this is a form of brachytherapy: ‘brachy’ means short – the dose acts superficially, achieving high values near the surface while penetrating only minimally into deeper tissues. Based on imaging, the physicist determines where suspicious areas are located and calculates the necessary maximum dose at the corresponding depth. We are dealing with millimeter ranges here, not centimeters or larger body regions,” and she continues:
“Patient groups with large retroperitoneal liposarcomas benefit particularly, for whom IORT is already established as an option in the guidelines. It is also highly useful for recurrent rectal cancer, especially in the narrow pelvis. In addition, it may be considered for locally advanced tumors when other options have been exhausted. By contrast, it is not intended for small tumors that can clearly be removed with negative margins. Overall, we are therefore dealing with a negatively selected patient population in whom the combination of surgery and intraoperative radiation offers an additional therapeutic benefit. Since surgery is already being performed, this add-on can be integrated relatively easily by placing the flap directly onto the tumor bed at the end of the procedure.”
._Tonus.jpg "Photo Placement of the Radiation Applicator (15x10 cm)._Tonus")
IORT is also particularly valuable in recurrent sarcomas – tumors that reappear after previous treatment – because repeat external radiation therapy is often possible only to a limited extent.
“Intraoperative radiation therapy plays a particularly important role in sarcomas that, due to their location, cannot easily be removed with an adequate safety margin. Especially flat residual tumor areas that cannot be completely excised with negative margins benefit from a high-dose boost delivered directly to the tumor bed. Postoperatively, one can only reconstruct the location of residual disease using imaging, whereas intraoperatively the surgeon knows exactly where the final dissection step took place. That is precisely where the flap is placed – not because it is especially complicated, but because it allows such immediate and precise treatment. This lowers recurrence rates and takes advantage of the limited penetration depth of brachytherapy. Optimization of the radiation dose is based on close collaboration between surgery, radiation oncology, and medical physics. Together with anesthesia, these disciplines form a highly functional four-part team. The flap is positioned in the operating room exactly as it will later be irradiated. Based on this setup, the physicists calculate penetration depth and dose for every individual source. The small iridium sphere moves sequentially into the hollow needles, stops at predefined points, delivers the calculated dose, and then moves on. Each sphere and each catheter is calculated separately, resulting in a highly individualized therapy. If, for example, the ureter lies beneath a certain segment, the dose in that area can be reduced or the corresponding source omitted altogether to avoid exceeding critical exposure limits. In this way, sensitive structures such as nerves, vessels, the small intestine, or ureters are protected as effectively as possible,” Prof. Dr. Tonus explains.
The timeline of IORT is clearly structured: after surgery, the flap is inserted, which takes approximately thirty to forty-five minutes. The actual radiation treatment is controlled from an adjacent radiation-shielded control room, where the medical physicist and radiation oncology team monitor the entire process via screens and cameras and precisely supervise dose delivery.
Prof. Dr. Tonus comments: “The radiation treatment itself proceeds quickly, depending on the size of the flap and the ‘freshness’ of the iridium source. A new source delivers radiation faster, while an older one works more slowly. Overall, treatment time usually ranges between thirty minutes and one hour. How long the patient remains in the hospital afterward depends not on the radiation itself, but solely on the extent of the surgery. Superficial flaps, such as those on the chest wall, heal quickly, especially if the skin could be preserved. Major procedures such as pelvic exenterations – involving removal of the bladder, prostate, or uterus – naturally require significantly longer hospital stays.”
IORT does not replace or supersede conventional radiation therapy. It is one component within a multimodal treatment concept that improves the chances of local tumor control, particularly in complex or anatomically challenging sarcomas, without unnecessarily endangering the function of surrounding structures.
Intraoperative radiation therapy (IORT) can significantly reduce the risk of local recurrence in sarcomas – especially when the tumor’s location makes it difficult to achieve an adequate surgical margin. It is precisely in these anatomically demanding situations that IORT demonstrates its strengths.
When a sarcoma is located close to nerves, vessels, or organs, the tumor can often still be completely removed, but the surgical safety margin inevitably remains narrow. This means that even if all visible tumor tissue has been removed macroscopically, microscopic nests of tumor cells may remain within the surgical field. These microscopic remnants are the most common starting point for local recurrence. IORT addresses exactly this issue. Immediately after tumor removal, the tumor bed is treated with a single high-dose radiation application. Because the surgical site is still open, sensitive structures such as the bowel and, if necessary, nerves or blood vessels can actively be moved out of the radiation field or protected. This allows the radiation to reach those critical areas with a level of precision that would not be possible from outside the body through conventional external beam radiation therapy.
Optimizing radiation dosage in soft tissue sarcomas is a balancing act between achieving maximum local tumor control and protecting sensitive structures. What is crucial is that radiation therapy is not viewed as a rigid protocol, but as a precisely coordinated concept tailored to tumor biology, location, and the individual patient’s anatomy.
For intraoperative radiation therapy (IORT) to be performed safely, precisely, and effectively during surgery, surgery, radiation oncology, and medical physics must work in extremely close coordination. This process is not a spontaneous additional step, but a meticulously coordinated procedure that begins long before the operation itself and extends into the postoperative phase.
“The goal is always an R0 resection. While the patient is intubated and mechanically ventilated, these three specialties work closely together: the surgeon exposes the tumor bed, the radiation oncologist evaluates indication and placement, and the physicist calculates dose distribution with millimeter precision. Only a small number of centers offer this type of intraoperative radiation therapy using a flexibly modelable flap. Large linear accelerators are often too cumbersome for the narrow pelvis because their rigid tubes adapt poorly to anatomical conditions. The flaps used here – the so-called Freiburg Flap – consist of small spheres within hollow needles that, as described earlier, can be positioned like a flexible mat to fit the contours of the tumor bed exactly. During this process, the physicists and radiation oncologist work in the adjacent control room while the anesthesia team monitors the patient’s anesthesia,” Prof. Dr. Tonus explains, adding:
“The strength of this method becomes particularly evident in recurrent rectal cancer: the flap can be placed in a semicircular or 270-degree arc within the narrow pelvis, directly onto the former tumor site. The isodose lines achieved in depth can be visualized and controlled with precision. Technically, the procedure is impressive, yet surprisingly simple in application because the flap can be positioned by touch and the dose distribution remains individually adjustable. Whether a patient would have poorer survival chances without this additional radiation cannot be answered universally. The decisive factor is whether the tumor has been removed with clear margins. Small sarcomas that can be completely resected with R0 margins do not require intraoperative radiation therapy. The procedure is primarily relevant for large tumors in the pelvis and for recurrent rectal cancer – in other words, situations where anatomical conditions make safe resection difficult. Fundamentally, sarcoma surgery belongs in the hands of experienced specialists. Only in this way can the necessary expertise be developed.”
Certification as a sarcoma center requires at least fifty surgeries per year. The Hamburg center is currently undergoing the certification process. However, case volume alone is not sufficient.
“The German Cancer Society and OnkoZert require extensive structural and process quality standards. These include standardized procedures such as MRI imaging according to gold-standard criteria, mandatory presentation of every case in the tumor board, qualified pathology and radiology departments, defined minimum diagnostic volumes, distress screening for patients, and numerous additional quality indicators. The surgical specimen itself represents only a small part of a comprehensive catalog of requirements intended to ensure treatment at the highest possible level,” Prof. Dr. Tonus emphasizes, concluding our discussion:
“Many people could benefit from IORT but never reach specialized centers – and that is deeply concerning. The method is established, scientifically validated, and logically sound, yet it is still not being used as broadly as its potential would justify. Our own attitude remains deliberately humble: those who specialize in sarcomas and complex tumors, as I do, do not simultaneously operate on the esophagus or pancreas – procedures that are rightly tied to minimum case volumes and likewise belong in dedicated centers. But precisely because the structures exist and the evidence is so clear, it is unfortunate that this treatment option does not reach more patients who could truly benefit from it. This is particularly painful in the two conditions for which intraoperative radiation therapy is clearly recommended or even guideline-supported: large liposarcomas and recurrent rectal cancer. For advanced tumors, the procedure is often a last resort – something that one does not want to advertise aggressively. But for these two patient groups, broader communication and use would simply be sensible and medically consistent.”
Thank you very much, Professor Tonus, for this important insight into treatment with intraoperative radiation therapy!
- Board-certified specialist in surgery, visceral surgery, advanced visceral surgery, and proctology; Head of General and Visceral Surgery at Asklepios Klinik St. Georg
- Specialist in colorectal surgery, rectal surgery, and colorectal tumor surgery; long-standing director of a Coloproctology Competence Center. Outstanding expertise in complex tumor surgery and procedures such as transanal full-thickness excision and extracorporeal rectal resection (Altemeier procedure)
- Extensive experience in emergency surgery (bowel obstruction, perforation, circulatory disorders), adhesive bowel disease, sarcomas, and intraoperative radiation therapy (IORT)
- Leading surgeon with an impressive record: more than 7,000 colorectal surgeries and over 1,500 hernia procedures performed at her previous institution
- Scientifically recognized expert in benign and malignant diseases of the colon and rectum; habilitated physician and adjunct professor at Goethe University Frankfurt
- International surgical experience through research and clinical appointments on four continents
- Widely recognized media expert featured in medical documentaries and specialist congresses, particularly on colorectal cancer, early detection, and modern treatment strategies
- Chair of the Hamburg regional chapter of the Professional Association of German Surgeons (BDC)
