RETROPERITONEAL TUMORS

Dr. AADITYA PRAKASH

DNB Resident, Radiation Oncology

BMCHRC, Jaipur

RETROPERITONEAL TUMOR CLASSIFICATION

10-15% of all soft tissue sarcomas

Median age at diagnosis is 6th decade (but wide range)

Most patients present with vague abdominal complaints :-

• 80% of patients are seen with an abdominal mass

• 50% of patients report pain at the time of presentation.

Tumors typically reach large size, with median diameter ~15cm

70% occur in abdomen, 30% occur in pelvis

5% likelihood of regional nodal involvement

RETROPERITONEAL SARCOMA

EPIDEMIOLOGY

RETROPERITONEAL SPACESuperior border: diaphragm

Inferior border: pelvic diaphragm

Lateral borders: at lateral edge of quadratus

lumborum, but lateral edge of 12th rib may be

considered, since it corresponds to the origin of

the transversus abdominus aponeurosis

Anterior border: parietal peritoneum

Posterior border: psoas, quadratus lumborum

muscles in abdomen, iliacus and obturator

internus and pyriformis in pelvis

RETROPERITONEAL SPACE

Composed predominately of lymphatics and loose connective tissue

Retroperitoneal organs: pancreas, kidney, adrenal glands, ureters.

Kidney, adrenal, and pancreatic tumors and malignant lympho-proliferative

processes in general do not fall into this category, even though they are located in

the same space.

Primary retroperitoneal tumors do not originate in anyretroperitoneal organ,

whether parenchymatous or not, but arise from actual tissues in the same space

or from embryonic rests found therein.

HISTOLOGY

Most common pathologies for retroperitoneal sarcoma are

liposarcoma and leiomyosarcoma.

Most common pathology in children is rhabdomyosarcoma.

Tumor grade prognostic for development of distant mets, local

recurrence, and decreased time to recurrence.

TNM STAGINGN.B:-Retroperitoneal and pelvic sarcomas are classified as deep tumors

*Superficial tumor is located

exclusively above the superficial

fascia without

invasion of the fascia;

Deep tumor is located exclusively

beneath the

superficial fascia, superficial to

the fascia with invasion of or

through the

fascia, or both superficial yet

beneath the fascia.

Stage IV in the AJCC sixth edition of 2002

Workup

Liposarcoma. Contrast-enhanced axial

CT shows large right retroperitoneal

liposarcoma (arrow) composed

predominantly of fat but also has areas

of soft tissue density and calcific

components.

Treatment

• Surgery (en bloc resection of the tumor + involved organs ) is the primary

TREATMENT modality for retroperitoneal sarcoma.

• Radical lymphadenectomy generally indicated only if gross nodal involvement.

• <70% amenable to complete surgical resection. Positive surgical margins are

associated with high local recurrence.

• ~50% of patients with GTR (R0 or R1) experience a recurrence, and overall local

recurrence rates may be as high as 95% with sufficient follow-up.

Surgery

• The primary factor in outcome is complete surgical resection, followed by the grade of

the lesion.

• MSKCC:- 10-year disease specific survival for those who had incomplete resection ( 18 % )

was substantially worse than that of patients who had complete resection (53 % for

those with negative margins and 54% for those with positive margins)

• The basis for unresectability is usually the presence of peritoneal implants, extensive

vascular involvement & distant metastases.

• Partial resections or debulking procedures have been performed, but there is no

evidence that partial resection improves survival. ( Jaques DP, Coit DG, Hajdu SI, et al )

Pre-op RT VS. Post-op RT• Preoperative EBRT for retroperitoneal sarcoma offers certain theoretical and practical

advantages :

High-dose treatment could minimize the risk of tumor implantation in the peritoneal cavity after a marginal resection by sterilizing a large number of tumor cells

partial tumor regression could facilitate grossly complete resection

there are favorable anatomic issues, including the tumor displacement of critical radiosensitive organs (bowel predominantly) away from the preoperative radiation field, thereby reducing toxicity and improving tolerance; and

an intact peritoneum offers a mechanical barrier to tumor seeding during the time radiotherapy is being administered before resection and division of these membranes.

• Bolla et al. found significantly worse 5-yr RT-related complication rate with PORT (23% vs. 0%) (IJROBP 2007)

Pre-op RT VS. Post-op RT

• Toronto Sarcoma Group/MD Anderson; 2006(Pawlik TM et al., Ann Surg Oncol

2006) :-

72 pts with intermediate- or high-grade retroperitoneal sarcoma. 75% were primary, and 25% were

recurrent.

Pts were treated preoperatively to a median dose of 45 Gy with concurrent low-dose doxorubicin.

89% underwent laparotomy with curative intent 4–8 wks after RT.

60% had an intraop or postop boost.

MEDIAN FOLLOW-UP:- 3.4 yrs

OUTCOME:-the recurrence rate was 52% after GTR. 5-yr LRFS was 60%, DFS was 46%, and OS was

61%.

CONCLUSION:-Results compared favorably to historical controls.

Pre-op RT VS. Post-op RT

• MD Anderson; 2003(Pisters PW, J Clin Oncol. 2003 Aug 15;21(16):3092-7.)

Phase I:- 35 patients, potentially resectable, intermediate or high grade retroperitoneal sarcoma. Doxorubicin QW with concurrent RT.

Dose escalation :-18/10, 30.6/17, 36/20, 41.4/23, 46.8/26, 50.4/28.

Sx: Total laparotomy in 83%. GTR (R0 or R1) in 90%.Then intra-op RT 15 Gy if R0 or R1 resection

Toxicity: Chemo-RT completed as outpatient in 89%, at 50.4 dose level (18% Grade 3-4 nausea).

Outcome: Preop EBRT can be administered to 50.4 Gy with C.I. doxorubicin.

ACOSOG Z9031

• "A randomized trial of preoperative radiation plus surgery versus surgery alone for localized primary retroperitoneal soft tissue sarcoma“

• The target accrual was 370 pts in 4.5 yrs. The primary endpoint was PFS. Unfortunately, this study closed due to poor accrual.

Intraoperative Radiation

• Mayo Clinic; 2002 "Use of intraoperative electron beam radiotherapy in the

management of retroperitoneal soft tissue sarcomas."

87 pts (primary or recurrent), median size 10 cm; all received max surgical

resection, preop XRT (median 48.6 Gy), IOERT (median 15 Gy)

5 yr OS affected by size >10cm (28% vs 60%), amount of residual tumor (37%

gross residual, 52% microscopic or no residual). No diff b/w primary vs

recurrent.

Local control 77% at 3yrs, 59% at 5 yrs. Local control affected by amt of

residual dz (41% gross, 60% microscopic, 100% no residual).

Intraoperative Radiation

• Massachusetts General Hospital retrospective review (Gieschen HL et al.,

IJROBP 2001) "Long-term results of intraoperative electron beam

radiotherapy for primary and recurrent retroperitoneal soft tissue

sarcoma."

• Included 29 pts:- 16 treated with IORT (10–20 Gy with intraop electrons)

and 13 treated without IORT. All pts received 45 Gy EBRT.

• LC improved with the addition of IORT (83% vs. 61%).

Intraoperative Radiation• NCI trial (Sindelar WF et al., Arch Surg 1993) :-

compared IORT + PORT to PORT alone for retroperitoneal STS.

35 pts were randomized to IORT (20 Gy) + postop EBRT (35–40 Gy) vs. PORT (50–55 Gy).

Both groups received chemo (doxorubicin/cyclophosphamide/methotrexate).

Follow-up :- 5 yrs

CONCLUSION:- there was no difference in OS between the groups (MS was 3.7 yrs with

IORT vs. 4.3 yrs with PORT). Local failure 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. 80% of pts with PORT.

Adjuvant Radiation

• University of Florida; 2005 (Zlotecki RA, Am J Clin Oncol. 2005 Jun;28(3):310-6.)

• Retrospective. 50 patients treated with surgery + RT (pre-op 38%, post-op 62%).

Pre-op 50.4/42 BID @ 1.2 Gy/fx; post-op RT <50 Gy in 1.8 Gy/fx

• Outcome: 5-year OS ->SM- 69% vs. SM+ 12% (SS); low grade 77% vs. high grade

34% (SS). Local recurrent pre-op 16% vs. post-op 47% (NS)

• Toxicity: Post-op RT more frequent complications, though none severe

• Conclusion: RT appears to improve probability of local control. Pre-op Rt may be

preferred

Adjuvant Radiation

• French Federation Cancer Sarcoma Group; 2001 (Stoeckle E, Cancer,

2001; 92(2): 359-68.)

• reviewed 145 pts with localized nonmetastatic retroperitoneal sarcoma.

• 65% underwent GTR, and 41% had adj RT.

• OUTCOME:-5-yr OS was 46%.5-yr LRC was 55% with adj RT vs. 23% with

surgery alone.

• CONCLUSION:-Randomized trial needed to evaluate place of RT for local

control.

Adjuvant Radiation

• Wayne State; 2002 Int J Radiat Oncol Biol Phys, 2002; 54(2): 514-9

• 60 pts, non-metastatic retroperitoneal sarcoma; all treated with

combined surgery + XRT. XRT was either given with EBRT alone (median

52.2 Gy) or EBRT + brachy boost (42 Gy EB + 16 Gy brachy).

• 5yr DFS 53%, 10yr DFS 44%. 5yr local control 71%, 10yr 54%. Margin

status significantly correlated w/ local control.

• CONCLUSION: margin status and local control very important for RP

sarcoma long term outcome.

Benefit of IMRT over 3D-CRT

• Emory; 2003(Koshy M, Sarcoma. 2003;7(3-4):137-48.)

Retrospective. 10 patients with RPS and 1 inguinal sarcoma.

Prescription 50.4 Gy. Comparison of 3D-CRT and IMRT.

Outcome: Significantly better dosimetry with IMRT

Conclusion: IMRT allowed enhanced tumor coverage and better

sparing of organs at risk

IMRT• Bossi A et al. (IJROBP 2007)

Prospective trial enrolling 18 pts with retroperitoneal sarcoma.

Pts were treated with neoadj. IMRT ( 50 Gy in 25 fractions of 2 Gy/fr.)

limited to the post abdominal wall, and planning was compared to

standard RT fields. All pts successfully completed RT and surgery.

There were 2 LRs, 1 within the high-dose region and 1 marginal

recurrence that would not have been covered by the standard CTV.

CONCLUSION:- limiting the CTV to the post abdominal wall is feasible.

RADIOTHERAPY TECHNIQUES

• Target Volumes and Organs of Interest Definition

■ GTV ->equals the imaging-defined tumor.

■ CTV -> 1.5 to 2 cm margin on GTV(may need to be reduced to protect

vital radiosensitive viscera.)

■ PTV -> expansion volume outside the CTV that accounts for setup

error and patient/organ movement.

DOSE/FRACTIONATION

■ Base preoperative/postoperative dose: 45 to 50 Gy/1.8 Gy/fr.

■ Postoperative setting:-EBRT beam boost of 5.4 to 9 Gy.

■ Intraoperative boost of 10 to 15 Gy using electron-beam therapy or

brachytherapy.

DOSE CONSTRAINTS

• LIVER :- V50 <20% ; V25 <50%

• U/L functioning kidney :- At least two-thirds of the volume should receive

<20 Gy (most important organ to save in case of single functional kidney).

• Stomach and bowel should be limited to a maximum dose of 45 Gy.

• Volume expansions should be minimized in regions where tolerance doses

to critical structures will be reached

NCCN

NCCN

TOXICITY

• ACUTE SYMPTOMS :- nausea, vomiting, diarrhea, skin redness, and

fatigue. Anemia, neutropenia, and thrombocytopenia may occur,

especially with large radiation fields that often involve the adjacent

spine.

• LONG-TERM SEQUELAE OF SURGERY AND RADIATION:-small bowel

enteritis, stricture, perforation, fistula, and obstruction. Development

of nephritis is possible after radiation doses >30 Gy, with resultant

hypertension.

Management of Locally RecurrentRetroperitoneal Sarcoma• Surgery.

• For patients presenting with a second or subsequent recurrence of retroperitoneal sarcoma, complete resection of retroperitoneal sarcoma is usually possible in 60% to 70 % . Combined with neoadjuvant systemic therapy or IMRT dependent on the histologic type or subtype, growth rate or time to local recurrence, and extent of disease.

• Isolated local recurrence is most common following complete resection of a primary retroperitoneal liposarcoma .

• Current chemotherapy is ineffective for the majority of patients with liposarcoma and toxicity limits adequate dosing by radiation therapy, complete surgical resection remains the most effective treatment modality.

• Palliative RT requires balancing expedient treatment with sufficient dose

expected to halt growth of ,or cause tumor regression. Numerous

clinical issues regarding rapidity of growth ,the status of systemic

disease, and the use of chemotherapy must be considered.

Recommended only for patients with unresectable or progressive

disease.

• Chemotherapy:-Intraperitoneal chemotherapy after debulking of

peritoneal metastases has been advocated.

THANK YOU