Retroperitoneal sarcoma

Question 1

What % of STS are retroperitoneal?

Answer 1

10%–15% of STS are retroperitoneal.

Question 2

What are the most common histologies of retroperitoneal sarcoma (RPS) in adults and children?

Answer 2

The 2 most common histologies for RPS in adults include liposarcoma and leiomyosarcoma.
The most common histology of RPS in children is rhabdomyosarcoma

Question 3

What % are malignant?

Answer 3

80% of retroperitoneal tumors are malignant.

Question 4

Describe the demographics of RPS.

Answer 4

There are a wide range of ages at presentation, but most pts are in their 50s with about equal numbers of men and women.

Question 5

What are the boundaries of the retroperitoneal space?

Answer 5

Boundaries of the retroperitoneal space:
Superior: diaphragm Inferior: pelvic diaphragm
Lateral: lat edge of quadratus lumborum, but lat edge of 12th rib is also considered b/c it corresponds to origin of transversus abdominis aponeurosis
Anterior: parietal peritoneum where it anchors to colon and small bowel
Posterior: muscular wall composed of psoas and quadratus lumborum in abdomen; iliacus, obturator internus, and pyriformis in pelvis

Question 6

Which organs are retroperitoneal?

Answer 6

Suprarenal (adrenal) glands, Aorta/IVC, Duodenum (2nd and 3rd parts), Pancreas, Ureters, Colon (ascending and descending), Kidneys, Esophagus, Rectum (Mnemonic: SADPUCKER)

Question 7

What is the typical presentation of pts with an RPS?

Answer 7

Pts typically present with vague abdominal complaints or are incidental findings.

Question 8

What is the DDx of a retroperitoneal ST mass?

Answer 8

The DDx of a retroperitoneal mass includes either malignant or benign
tumors.
Malignant etiology includes:
1. Sarcoma
2. Gastrointestinal stromal tumor
3. Lymphoma
4. Germ cell tumor
5. Metastatic testicular cancer
6. Malignant peripheral nerve sheath tumor
7. Paraganglioma
Benign etiology includes:
1. Desmoid tumor
2. Lipoma
3. Peripheral nerve sheath tumor
4. Teratoma
5. Paraganglioma
6. Castleman Dz
7. Retroperitoneal fibrosis

Question 9

What is the median diameter of RPS at presentation?

Answer 9

The median diameter of retroperitoneal STS is 15 cm.

Question 10

How is RPS staged according to AJCC (8th edition, 2017) staging?

Answer 10

T1: ≤5 cm
T2: >5 cm and ≤10 cm
T3: >10 cm and ≤15 cm
T4: >15 cm
N1: Regional LN mets
M1: DMs
Stage IA: T1, N0, Grade 1-X
Stage IB: T2–4, N0, Grade 1-X
Stage II: T1, N0, Grade 2–3
Stage IIIA: T2, N0, Grade 2–3
Stage IIIB: T3–4, N0, Grade 2–3 or any T, N1
Stage IV: M1

Question 11

Do all pts with suspected RPS require a preop Bx?

Answer 11

No. Preop Bx is not required if the suspicion for RPS is high. However, CTguided
core Bx should first be performed in pts undergoing neoadj therapy.

Question 12

What imaging studies should be performed to stage RPS?

Answer 12

Recommended staging studies for RPS include CT C/A/P with contrast and optional MRI.

Question 13

What is the primary Tx modality for sarcoma RPS?

Answer 13

Sg (en bloc resection of the tumor and involved organs with the goal of attaining –SMs)

Question 14

What is the most important Tx factor which predicts survival for RPS?

Answer 14

Postop SM status is the most important factor in predicting survival. MSKCC analysis of >500 pts showed MS = 103 mos if GTR vs. only 18 mos for less than GTR. (Lewis JJ et al., Ann Surg 1998)

Question 15

What are the Tx paradigms for RPS?

Answer 15

Note: Postop EBRT is discouraged relative to preop. Consideration of IORT boost for + SMs may be given.

1. Sg (+/– IORT)
2. Neoadj RT and/or chemo → Sg (+/– IORT)
3. Sg (+/– IORT) → adj RT and/or chemo

Question 16

What is the role of CRT in pts with RPS?

Answer 16

There is controversy. A phase I study (Pisters et al., JCO 2003) evaluated concurrent preop doxorubicin and escalating RT. Preop 50.4 Gy w/doxorubicin was found feasible. 4 pts required hospitalization and 18% had
grade 3–4 nausea. A recent phase I–II study (Gronchi et al., Eur J Cancer 2014) evaluated the addition of high-dose, long-infusion ifosfamide and RT as preop Tx for resectable RPS. The combination was feasible in 2/3rds of pts.

Question 17

What % of RPS are amenable to a GTR?

Answer 17

(50%–67%) of RPS are amenable to a GTR.

Question 18

Is recurrence after Sg for RPS more likely to be local or distant?

Answer 18

Most recurrences after Sg for RPS are local.

Question 19

What is the LR rate after GTR (R0 or R1) for RPS?

Answer 19

LR ranges from 50%–95% in pts who have undergone GTR for RPS.

Question 20

Summarize the argument in favor of preop RT over PORT.

Answer 20

Preop RT may be sup to PORT for RPS b/c it allows for better tumor volume definition, displacement of normal viscera by tumor, smaller Tx fields, intraop tumor seeding theoretically reduced, and the potential radiobiologic
advantage of having normal vasculature/oxygenation in place that, extrapolating from extremity sarcoma data, make 50 Gy preop comparative to 60–66 Gy postop. No RCT exists comparing preop RT vs. PORT, however,
Ballo et al. found significantly worse 5-yr RT related complication rate with PORT (23% vs. 0%). (IJROBP 2007)

Question 21

Is there a benefit of adding IORT after the surgical management of RPS?

Answer 21

Possibly. There are at least 2 studies that suggest IORT improves LC when added to EBRT, but it is unclear if this improves OS. An NCI trial (Sindelar WF et al., Arch Surg 1993) compared PORT to PORT + IORT for RPS. 35 pts were randomized to postop EBRT (35–40 Gy) vs. PORT
(50–55 Gy) + IORT (20 Gy) coadministered with Misonidazole. Chemo (doxorubicin/ cyclophosphamide/Mtx) was used for a portion of the trial. There was a significant improvement in “in-field” LR with IORT (40% IORT vs. 80% PORT). RT enteritis occurred in 13% of pts with IORT and 50% of pts with PORT. Peripheral neuropathy was found in 60% of pts
with IORT vs. 5% of pts with PORT. 22 (39%) MDACC pts rcvd 15 Gy IORT after 18 Gy–50.4 Gy in a prospective trial of neoadj RT and low-dose doxorubicin with favorable
results. However, there was no association of DFS or OS with IORT. (Pawlik et al.)

Question 22

Summarize the outcomes of the Toronto Sarcoma Group and the MDACC prospective trials of preop EBRT for localized intermediate- or high-grade
RPS.

Answer 22

The Toronto Sarcoma Group and the MDACC prospective trials enrolled 72 pts with intermediate- or high-grade RPS. 75% were primary, and 25% were
recurrent. Pts were treated preop to a median dose of 45 Gy (18–50.4 Gy). The MDACC pt population also rcvd concurrent low-dose doxorubicin. 89% underwent laparotomy with curative intent 4–8 wks after RT. 60% had an intraop/postop boost. (Due to high morbidity, modification to selective brachytherapy to the lower abdomen/pelvis only was adopted.) At median f/u
of 3.4 yrs, 52% of pts with GTR developed recurrent Dz. 5-yr LRFS was 60%, DFS was 46%, and OS was 50%. (Pawlik TM et al., Ann Surg Oncol 2006) Results compared favorably to historical controls of Sg alone.

Question 23

Are there any prospective randomized trials examining the role of RT in the management of RPS?

Answer 23

ACOSOG Z9031 randomized pts to Sg alone vs. preop RT + Sg for primary RPS. The target accrual was 370 pts in 4.5 yrs. The primary endpoint was PFS. This study closed d/t poor accrual.
The STRASS trial (conducted by the EORTC) is randomizing pts to Sg alone vs. preop RT + Sg. Accrual is complete and results anticipated shortly.

Question 24

What EBRT dose is typically used for preop RT for RPS?

Answer 24

RPS is typically treated 45–50.4 Gy preop. On protocol or at experienced centers, a SIB to 57.5–63 Gy may also be utilized.

Question 25

Is a preop EBRT boost to a region of presumed high risk for + SMs effective?

Answer 25

This is uncertain. The efficacy of limited RT or an SIB is under investigation. There is an ongoing multicenter phase I–II trial of preop imageguided photon IMRT and proton RT with SIB to the high-risk margin sponsored by Mass General Hospital.

Question 26

Is there a benefit of IMRT over 3D-CRT for the preop management of RPSs?

Answer 26

Yes, in general pts should be treated using IMRT to limit dose to surrounding tissue. The Emory retrospective review compared 3D-CRT with IMRT for 10 pts with RPS and showed improved tumor coverage with better sparing of organs at risk with IMRT. (Koshy M et al., Sarcoma 2003)

Question 27

What are the recommended expansions for RPS?

Answer 27

As recommended by a recent consensus panel
CTV = GTV + 1.5 cm
Edit CTV as follows:
Bone: 0 mm
Renal and hepatic interfaces: 0 mm
Bowel and air cavity: 5 mm
Skin surface: 3 mm
If tumor extends through inguinal canal, add 3 cm distally (as per extremity STS)

The preliminary consensus further details coverage of surrounding organs and Tx volume expansions per motion management technique at the time of CT-simulation. (Baldini et al., IJROBP 2015)

Question 28

What are acute and late toxicities associated with RT for RPS?

Answer 28

Acute and subacute toxicities: n/v, diarrhea, fatigue, erythema, wound complications, duodenitis/gastritis
Late toxicities: SBO (as well as stenosis and perforation), fistula, kidney failure, RILD, myelopathy, peripheral neuropathy, 2nd malignancy