A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

Roeder, Falk; Ulrich, Alexis; Habl, Gregor; Uhl, Matthias; Saleh-Ebrahimi, L.; Huber, Peter E.; Schulz-Ertner, Daniela; Nikoghosyan, Anna; Alldinger, Ingo; Krempien, Robert; Mechtersheimer, Gunhild; Hensley, Frank W.; Debus, Jürgen; Bischof, Marc

doi:10.1186/1471-2407-12-287

Cited by 58 publications

(29 citation statements)

References 23 publications

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“…This uncertainty is especially important given the potential for rare—albeit clinically meaningful—radiation toxicities, such as gastrointestinal upset/dehydration, intestinal obstruction, ureteral stricturing, leukopenia, and anemia/ bleeding. 3,15,16 …”

Section: Discussionmentioning

confidence: 99%

“…10 In the interim, little survival data have surfaced regarding preoperative RT for RPSs. Published reports in that time have included several additional single-institution reviews, 8,13,15,17,18 2 prospective studies evaluating survival only among patients treated with radiation, 16,19 and 2 preliminary trials evaluating the safety and efficacy of concomitant chemoradiation therapy 20,21 (Table 5). Here, we utilize the NCDB to help better define the impact of neoadjuvant RT for this malignancy and to provide more meaningful survival data for patients treated with preoperative RT.…”

Section: Discussionmentioning

confidence: 99%

“…8,15,18,19 Moreover, advances in radiation technology, such as intensity-modulated RT, have improved the ability to focus the high-dose radiation region to the target to minimize treatment toxicity. 16,18 Third, the pathologic diagnosis of sarcomas—including histologic subtyping and grading—may not be uniform across centers. However, our subgroup analysis of leiomyosarcomas—a tumor that can specifically be distinguished by its expression of smooth muscle markers—corresponded well with our overall analysis, increasing our confidence that differences in pathologic evaluation were not a major limitation.…”

Section: Discussionmentioning

confidence: 99%

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Long-term Oncologic Outcomes After Neoadjuvant Radiation Therapy for Retroperitoneal Sarcomas

Nussbaum¹,

Speicher²,

Gulack³

et al. 2015

Annals of Surgery

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Objective To evaluate long-term survival among patients undergoing radiation therapy (RT), followed by surgical resection of retroperitoneal sarcomas (RPS). Background Despite a lack of level 1 evidence supporting neoadjuvant RT for RPS, its use has increased substantially over the past decade. Methods The 1998–2011 National Cancer Data Base was queried to identify patients who underwent resection of RPS. Subjects were grouped by use of neoadjuvant RT. Perioperative variables and outcomes were compared. Multivariable logistic regression was performed to assess predictors of neoadjuvant RT. Groups were propensity matched using a 2:1 nearest neighbor algorithm and short-term outcomes were compared. Finally, long-term survival was evaluated using the Kaplan-Meier method, with comparisons based on the log-rank test. Results A total of 11,324 patients were identified. Neoadjuvant RT was administered to 696 patients (6.1%). During the study period, preoperative RT use increased from 4% to nearly 15%. Male sex, tumor size larger than 5 cm, treatment at an academic/research program, and higher tumor grade all predicted neoadjuvant RT administration. After propensity matching, the only difference in baseline characteristics was the use of neoadjuvant chemotherapy. Although neoadjuvant RT was associated with a higher rate of negative margins (77.5% vs 73.0%; P = 0.014), there was no corresponding improvement in 5-year survival (53.2% vs 54.2%; P = 0.695). Conclusions Despite the increasing use of neoadjuvant RT for patients with RPS, the survival benefit associated with this treatment modality remains unclear. Continued investigation is needed to better define the role of RT among patients with RPS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Long-term Oncologic Outcomes After Neoadjuvant Radiation Therapy for Retroperitoneal Sarcomas

Nussbaum¹,

Speicher²,

Gulack³

et al. 2015

Annals of Surgery

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“…Similarly to extremity STS, surgery remains the cornerstone of curative intent treatment in retroperitoneal sarcoma [56, 57]. However, in contrast to extremity sarcoma, local progression remains the dominant pattern of failure with roughly 50–80% of the patients failing locally even after gross total resection [52, 58–62].…”

Section: Introductionmentioning

confidence: 99%

“…However, in contrast to extremity sarcoma, local progression remains the dominant pattern of failure with roughly 50–80% of the patients failing locally even after gross total resection [52, 58–62]. Resection margin is a strong prognostic factor [59–61] but wide margins are usually not achievable [19, 56, 57, 60]. This builds up (at least theoretically) an even stronger rationale for the addition of radiation therapy than in extremity sarcoma.…”

Section: Introductionmentioning

confidence: 99%

Intraoperative radiation therapy (IORT) in soft-tissue sarcoma

Roeder

Krempien

2017

Radiat Oncol

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Soft-tissue sarcoma (STS) represent a rare tumor entity, accounting for less than 1% of adult malignancies. The cornerstone of curative intent treatment is surgery with free margins, although the extent of the surgical approach has been subject to change in the last decades. Multimodal approaches usually including radiation therapy have replaced extensive surgical procedures in order to preserve functionality while maintaining adequate local control. However, the possibility to apply adequate radiation doses by external beam radiation therapy (EBRT) can be limited in some situation especially in case of directly adjacent organs at risk with low radiation tolerance. Application of at least a part of the total dose via intraoperative radiation therapy (IORT) with a single fraction during the surgical procedure may overcome those limitations, because radiosensitive structures can be moved out of the radiation field resulting in reduced toxicity while the enhanced biological effectivity of the high single dose improves local control. The current review summarizes rationale, techniques, oncological and functional outcomes including possible pitfalls and associated toxicities based on the published literature for IORT focusing on extremity and retroperitoneal STS. In extremity STS, combination of limb-sparing surgery, IORT and pre- or postoperative EBRT with moderate doses consistently achieved excellent local control rates at least comparable to approaches using EBRT alone but usually including patient cohorts with higher proportions of unfavourable prognostic factors. Further on, IORT containing approaches resulted in very high limb preservation rates and good functional outcome, probably related to the smaller high dose volume. In retroperitoneal STS, the combination of preoperative EBRT, surgery and IORT consistently achieved high local control rates which seem superior to surgery alone or surgery with EBRT at least with regard to local control and in some reports even to overall survival. Further on, preoperative EBRT in combination with IORT seems to be superior to the opposite combination with regard to local control and toxicity. No major differences in wound healing disturbances or postoperative complication rates can be observed with IORT compared to non-IORT containing approaches. Neuropathy of major nerves remains a dose limiting toxicity requiring dose restrictions or exclusion from target volume. Gastrointestinal structures and ureters should be excluded from the IORT area whenever possible and the IORT volume should be restricted to the available minimum. Nevertheless, IORT represents an ideal boosting method if combined with EBRT and properly executed by experiences users which should be further evaluated preferably in prospective randomized trials.

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