Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 
LETTER TO THE EDITOR
Ahead of print publication  

STRASS trial: Preoperative radiotherapy in retroperitoneal sarcoma: A commentary


1 Department of Radiation Oncology, AIIMS, New Delhi, India
2 Department of Medical Oncology, AIIMS, New Delhi, India

Date of Submission06-Aug-2019
Date of Acceptance12-Sep-2019
Date of Web Publication13-Oct-2020

Correspondence Address:
Sameer Rastogi,
Department of Medical Oncology, AIIMS, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_573_19



How to cite this URL:
Shishak S, Rastogi S, Kalra K, Parisa M. STRASS trial: Preoperative radiotherapy in retroperitoneal sarcoma: A commentary. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 20]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=298077



Sir,

Surgical resection is the standard of care for localized operable retroperitoneal sarcoma (RPS). Unlike extremity soft-tissue sarcoma,[1] the role of preoperative radiotherapy (RT) in RPS has remained largely unanswered. As local recurrence is the major cause of death in most of the RPS cases, there is increasing interest in the role of preoperative RT. The advantages of preoperative RT over postoperative RT are smaller treatment volumes, easier tumor volume delineation, radiobiologically superior normal vasculature/oxygenation, and lesser toxicities to normal organs such as bowel. However, patient recruitment into clinical trials for RPS has historically been limited by the rarity of this disease. The only randomized multicentric trial conducted in the USA (ACOSOG Z9031) which attempted to answer the role of preoperative RT in RPSs was closed due to slow patient accrual.[2]

In 2016, a propensity score-matched analysis of a nationwide clinical database published in the Lancet Oncology by Nussbaum et al.[3] included over 9000 patients. This database study showed that RT was associated with improved overall survival (OS) compared with surgery alone when delivered either preoperatively or in postoperative setting. However, a propensity matched analysis is not a replacement for a properly conducted randomized trial.[4]

This year, A trial looking at radiotherapy and surgery for sarcoma (STRASS), a Phase III randomized study of preoperative RT plus surgery versus surgery alone for patients with RPS, European Organisation for Research and Treatment of Cancer protocol (62092-22092), was presented at the American Society of Clinical Oncology2019. This is the first trial with transatlantic collaboration that randomized 256 RPS patients to preoperative RT followed by surgery versus surgery alone, with the primary end point being abdominal recurrence-free survival (ARFS) which was defined by one of the following events:

  1. During or after surgery:


    1. Local relapse after macroscopically complete resection
    2. Peritoneal sarcomatosis found at laparotomy
    3. Macroscopic local disease left behind at laparotomy (R2).


  2. Before surgery:


    1. Development of distant metastases while on preoperative RT
    2. Local progression of primary tumor while on preoperative RT
    3. Becoming American Society of Anesthesiologist score = 3, involvement of superior mesenteric artery or aorta or bone.


In July 2017, the Independent Data Monitoring Committee (IDMC) recommended a sensitivity analysis in which local progression on RT was not regarded as a primary end point event for patients who subsequently achieve a complete surgical resection.

Majority of the patients (75%) had liposarcoma (LPS) (well-differentiated LPS: 33.1%, dedifferentiated LPS [DDLPS]: 39.5%, and other LPS: 1.9%), whereas leiomyosarcoma (LMS) constituted just 14.3% of the patient population. RT dose was 50.4 Gy/28#/5.5 weeks delivered by intensity-modulated radiation therapy in a majority of patients (n = 120, 95%) and three-dimensional conformal RT in 5% (n = 7) of patients. The only Grade 4 RT toxicity was lymphopenia in thirty patients (23%).

After a median follow-up of 43 months, the ARFS in preoperative RT was 60.4% versus 58.7% in surgery arm (P = 0.95). With the IDMC-recommended modification, there was ARFS benefit in the LPS subgroup only. High-grade sarcomas and LMS did not benefit from preoperative RT. There was no significant OS difference in both arms.

The failure of this study could be due to a multitude of reasons. First, RPS cases are an extremely heterogeneous population, with different biologic behavior depending on the histology, subtypes, and grade. In well-differentiated LPS, the local recurrence rate is about 4%–5% per year. Hence, the median follow-up of 43 months as shown in this study might be inadequate for this subgroup to have significant events. Grade 1–2 DDLPS cases have rapid local failures (20% at 2 years and 40% at 5 years) with distant metastasis rate at 5 years <10%, whereas Grade 3 DDLPS and LMS have 50% risk of distant metastasis. The benefit in ARFS in LPS subgroup unlike LMS could be due to the recurrence pattern of LPS which is commonly local versus LMS which recurs at distant sites,[5] as shown in [Table 1].
Table 1: Histologic subtypes and pattern of recurrences

Click here to view


Another flaw was that grades were not available for one-fourth of the patients, which is unexpected from a randomized controlled trial. Along with this, the statistical proposition to show an absolute increase of 20% in the 5-year ARFS rate seems too optimistic a hypothesis. Simultaneously, as it is a multicentric study, there needs to be centralized assessment of surgery as the expertise in different institutes might lead to different perception of resectable disease.

Despite all its inherent flaws and limitations, it is still a highly laudable effort in terms of transatlantic collaboration in a rare disease such as this. The study has widened our perspective and encourages the pursuance of future trials, with the hope of elucidating the role of preoperative RT in RPS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
O'Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial. Lancet 2002;359:2235-41.  Back to cited text no. 1
    
2.
Surgery With or Without Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Retroperitoneum or Pelvis - Full Text View. Available from: https://clinicaltrials.gov/ct2/show/NCT00091351. [Last accessed on 2019 Aug 06].  Back to cited text no. 2
    
3.
Nussbaum DP, Rushing CN, Lane WO, Cardona DM, Kirsch DG, Peterson BL, et al. Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: A case-control, propensity score-matched analysis of a nationwide clinical oncology database. Lancet Oncol 2016;17:966-75.  Back to cited text no. 3
    
4.
Streiner DL, Norman GR. The pros and cons of propensity scores. Chest 2012;142:1380-2.  Back to cited text no. 4
    
5.
Dingley B, Fiore M, Gronchi A. Personalizing surgical margins in retroperitoneal sarcomas: An update. Expert Rev Anticancer Ther 2019;19:613-31.  Back to cited text no. 5
    



 
 
    Tables

  [Table 1]



 

 
Top
 
 
  Search
 
     Search Pubmed for
 
    -  Shishak S
    -  Rastogi S
    -  Kalra K
    -  Parisa M
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  >Article Tables
  In this article
>References

 Article Access Statistics
    Viewed131    
    PDF Downloaded1    

Recommend this journal