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The following publications about DSRCT are for informational purposes only. Please see your doctor to discuss a specific patient concern. Note that the primary purpose of these publications are for the medical profession and may not pertain to an individual patient. Also, please be note the dates on publications as information about treatment of this disease can become dated as new information is discovered.
Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 28, No 15_suppl (May 20 Supplement), 2010: 10094 © 2010 American Society of Clinical Oncology
Analysis of prognostic factors of pediatric-type sarcomas in adult patients
H. Ahn, J. Um, J. Lee, W. Kim, D. Lim and J. Park
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Radiation-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Background: Pediatric-type sarcomas such as Ewing's sarcoma/primitive neuroectodermal tumor family (EWS/PNET) and rhabdomyosracoma (RMS) are relatively uncommon in adult patients (pts). Optimal treatment strategies for this population remain controversial and there have been debates on whether adults do worse than pediatric pts with the same stage of disease.
Methods: To identify prognostic factors, we retrospectively reviewed clinical data on pts with pediatric type sarcoma older than 15 years at a single institution.
Results: Seventy-five consecutive patients from February 1995 to October 2005 were identified from the database at the Samsung Medical Center, Seoul, Korea. Forty-five patients (60.0%) of 75 patients were male. Median age of patients was 30-year old with range of 15–74. Forty patients (53.3%) were diagnosed as EWS/PNET, 32 patients (42.7%) as RMS and 3 patients (3%) as DSRCT. Median overall survival (OS) for all patients was 39 months (95% CI. 13.0-65.0 months) and median event-free survival (EFS) for all patients was 19 months (95% CI. 5.0-33.0). Multivariate analysis revealed that age over 30, IRS III/IV and poor performance status were significant independent prognostic factors for poor OS, whereas IRS III/IV was the only prognostic factors for EFS. In subset analysis, only pts younger than 30 years showed favorable outcomes in pts group with IRS I/II.
Conclusions: Although the limits of this retrospective study are self-evident, we identified the prognostic variables enable risk-adapted therapies for this rare adult sarcoma group, which should be further investigated. Also, our data would suggest that pediatric treatment protocols are feasible for the adult pts so optimal therapy should be given to the pts.
Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 27, No 15S (May 20 Supplement), 2009: 10016 © 2009 American Society of Clinical Oncology
Elevated expression of VEGFR-2 and VEGFA in desmoplastic small round cell tumor (DSRCT) and activity of bevacizumab (avastin) and irinotecan in a xenograft model of DSRCT
H. D. Magnan, T. Chou, M. P. LaQuaglia, W. Gerald, M. Ladanyi and M. S. Merchant
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Desmoplastic small round cell tumor (DSRCT) is an aggressive tumor with poor response to multimodality therapies. Given the vascular nature of many DSRCT, we sought to determine if VEGF targeting could be effective in a preclinical model of DSRCT. Methods: RNA was extracted from frozen tumor samples (DSRCT, alveolar soft part sarcoma, alveolar rhabdomyosarcoma, synovial sarcoma, and Ewing sarcoma) and a human DSRCT cell line, JN-DSRCT. Microarray profiling utilized Affymetrix U133A/B or Affymetrix U133 Plus 2.0 chips. DSRCT xenografts were established by intramuscular injection of 20 million JN-DSRCT cells into the lower extremity of SCID/bg mice. A primary tumor developed within 8 - 12 weeks with concomitant development of abdominal metastases. Mice were treated during primary tumor growth with bevacizumab (5ug/kg IP weekly), irinotecan (2.5mg/kg IP x10 days q3 weeks), or a combination of both. Results: Microarray data demonstrated an average of 4.5 times higher RNA expression of VEGFR-2 (KDR) in DSRCT tumor samples as compared to the other translocation-associated sarcomas (p = 3.6 E-12). VEGFR-2 was highly expressed in the JN-DSRCT line as compared to other sarcoma lines. VEGFA was also highly overexpressed in the DSRCT line and tumor samples when compared to the other translocation-associated sarcomas (2.5 times, p = 1.1E-10). Xenografts treated with bevacizumab had slowed growth over 100 days compared to control groups (volume of 0.52 mm3 vs 1.52, p = 0.002). Marked long term regressions were evident following treatment with the combination of irinotecan plus bevacizumab compared with irinotecan alone (0.12mm3 vs 0.44 at 100 days, p < 0.0001). Conclusions: VEGFR-2 and VEGFA are overexpressed in DSRCT. DSRCT xenografts were highly responsive to bevacizumab or bevacizumab plus irinotecan. Taken together, the expression data and the sustained response of DSRCT xenografts to bevacizumab suggest that VEGF-dependent angiogenesis is important for DSRCT tumor biology and represents an attractive target for therapy. These studies suggest that irinotecan and bevacizumab should be considered for inclusion in clinical trials for the treatment of DSRCT.
No significant financial relationships to disclose.
Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Supplement), 2008: 10533 © 2008 American Society of Clinical Oncology
Continuous daily dosing (CDD) of sunitinib (SU) in patients with metastatic soft tissue sarcomas (STS) other than GIST: Results of a phase II trial
M. L. Keohan, J. A. Morgan, D. R. D’Adamo, D. Harmon, J. E. Butrynski, A. J. Wagner, G. K. Schwartz, R. G. Maki, G. D. Demetri and S. George
Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA
Background: SU is an oral multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET approved multinationally for treatment of imatinib-resistant/intolerant GIST. SU demonstrated early evidence of activity in sarcomas other than GIST during phase I testing. The current phase II study was designed to examine the clinical activity of CDD of SU in pts with advanced STS other than GIST. Methods: Pts with metastatic and/or locally advanced STS, measurable disease, ECOG PS 0–1 and ≤3 prior chemotherapy regimens were eligible. Pts are enrolled in 1/2 study arms: histologies that have shown responses to TKIs (Arm A) or histologies that have not (Arm B). Using a Simon 2-stage design, 21+20 patients will be recruited per arm based on ORR. The treatment regimen is administered as CDD of SU (37.5 mg) in 4-wk cycles. The primary endpoint is ORR per arm based on RECIST. Secondary endpoints include progression-free rate (CR+PR+SD) at 16 and 24 wks and OS. FDG-PET response before and after 2 wks of therapy was assessed in 21 pts and is reported in a separate abstract by Van den Abbeele et al (ASCO 2008). Results: As of Jan. 2008, 41 evaluable pts were enrolled, 20 in Arm A and 21 in Arm B (17 M, 24 F, ages 18 - 86). Results are available for 39 pts. In Arm A, there are no PRs or CRs; 11/20 pts had SD as best response (hemangiopericytoma 2, pulmonary intimal sarcoma 1, leiomyosarcoma 5, chordoma 2, angiosarcoma 1). 3/11 remain stable at wk 16 (range 16 - 32). In Arm B, 1 pt with desmoplastic small round-cell tumor (DSRCT) exhibited a PR at cycle 2 that continues at wk 32. There are no CRs. 6/19 pts had SD as best response (giant cell tumor 1, synovial 1, alveolar soft part sarcoma 1, DSRCT 1, well-/de-differentiated liposarcoma 2). 4 pts remain stable at wk 16. Grade 3 AEs include hematologic toxicities (19), diarrhea (5), mucositis (6), hand-foot syndrome (3), GI bleed (1) and seizure (1). One grade 4 event occurred: GI hemorrhage, duodenal ulcer. Conclusions: CDD of SU 37.5 mg has demonstrable activity in pts with certain subtypes of STS. Certain histologies such as DSRCT, giant cell tumor and solitary fibrous tumor/hemangiopericytoma may achieve prolonged disease control. Larger cohorts of these specific subtypes are needed to confirm this benefit.
1: Cancer Lett. 2007 Mar 8;247(1):84-90. Epub 2006 May 30. Links A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene.
Werner H, Idelman G, Rubinstein M, Pattee P, Nagalla SR, Roberts CT Jr.
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, 69978 Tel Aviv, Israel.
Desmoplastic small round cell tumor (DSRCT) is a primitive sarcoma characterized by a recurrent chromosomal translocation, t(11;22)(p13;q12), which fuses the 5' exons of the EWS gene to the 3' exons of the WT1 gene. EWS-WT1 chimeras are heterogeneous as a result of fusions of different regions of the EWS gene to the WT1 gene. We report here a rare and novel EWS-WT1 variant, EWS-WT1 5/10, in a 6-year-old boy diagnosed with DSRCT and analyze the potential transactivation effect of the fusion oncoprotein. The predicted product is comprised of the N-terminal transactivation domain of EWS and lacks any sequence derived from the WT1 gene product. Nonetheless, the truncated protein was able to stimulate expression of the insulin-like growth factor-I receptor gene, a potent antiapoptotic receptor tyrosine kinase with potentially important roles in DSRCT etiology. These findings raise the possibility that the oncogenic potential of EWS-WT1 fusions is not necessarily a consequence of the fusion protein product per se.
PMID: 16730884 [PubMed - in process]
2. British Sarcoma Group Conference: Size does not matter! - Predictors of response and survival in desmoplastic small round blue cell tumours (DSRBCT)
Androgen and c-Kit receptors in desmoplastic small round cell tumors resistant to chemotherapy: novel targets for therapy. 2006 Aug 3
- Fine RL, Shah SS, Moulton TA, Yu IR, Fogelman DR, Richardson M, Burris HA, Samuels BL, Assanasen C, Gorroochurn P, Hibshoosh H, Orjuela M, Garvin J, Goldman FD, Dubovsky D, Walterhouse D, Halligan G.
College of Physicians and Surgeons of Columbia University, New York-Presbyterian Medical Center and Morgan Stanley Children's Hospital, New York, NY, USA.
PURPOSE: Desmoplastic small round cell tumor (DSRCT) is a highly fatal, mainly peritoneal cell origin cancer which predominantly affects young adult males. This predilection in young males led us to examine the role of androgen receptors (AR), testosterone, and growth factors in the biology of DSRCT. METHODS: Slides were prepared from 27 multi-institutional patients all with end-stage DSRCT. Slides were stained for AR, c-Kit, various growth factors, and drug resistance-associated proteins. Immunohistochemical (IHC) expression was scored semi-quantitatively. Western blot and MTT studies were performed to validate the IHC findings of over-expression of the AR and its functional status by stimulation of growth by dihydrotestosterone, respectively. Six patients with positive AR status were treated solely with combined androgen blockade (CAB) as used for prostate cancer. RESULTS: Twenty-two patients were male (81%) and five were female (19%) with a median age at diagnosis of 23. All patients had failed at least two prior multi-agent chemotherapy regimens and 44% had progressed after autologous stem cell transplant. DSRCT samples from 10 of 27 patients were >/=2+ IHC positive for AR (37%,P = 0.0045) and 7 of 20 patients were >/=2+ IHC positive for c-Kit (35%, P = 0.018). We found elevated IHC expression of GST-pi, MRP and thymidylate synthase in smaller subsets of patients. In vitro studies for AR by Western blot and stimulation of growth by dihydrotestosterone in MTT assays suggest that the AR in DSRCT cells is functional. Six patients with positive AR status were treated with CAB alone and three of six attained clinical benefit (1-PR, 1-MR, 1-SD) in a range of 3-4 months. The three patients who responded to CAB had normal testosterone levels before CAB, while the three who did not respond to CAB had baseline castrate levels of testosterone. CONCLUSIONS: DSRCT has significant IHC expression of AR and c-Kit in heavily pre-treated patients. The presence of significant AR expression in 37% suggests that these patients could possibly respond to CAB. The significance of c-Kit expression in 35% of DSRCT patients is unknown and warrants further investigation.
PMID: 16896931 [PubMed - as supplied by publisher]
2. Coll Physicians Surg Pak. 2006 Sep;16(9):614-6. Desmoplastic small round cell tumor.Yaqoob N, Hasan SH. Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi. firstname.lastname@example.org
Desmoplastic small round cell tumour (DSRCT) is a unique, highly aggressive neoplasm that chiefly affects adolescent male and young adults and most frequently presents as a large abdominal mass with widespread peritoneal involvement at the time of diagnosis. Histologically, it is composed of nests of small, undifferentiated round or oval hyperchromatic cells embedded in abundant desmoplastic stroma. Co-expression of epithelial, mesenchymal, and neural antigens in the same cell provides evidence of origin from a primitive pluripotent stem cell with multiphenotypic differentiation. A multidisciplinary treatment including high-dose chemotherapy, aggressive debulking surgery, radiation and myeloablative chemotherapy with stem cell rescue might be the proper approach to treat this rare malignancy and may improve progression-free survival.
PMID: 16945240 [PubMed - indexed for MEDLINE]
3. Bone Marrow Transplant. 2006 Jan;37(2):175-81. Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors.Fraser CJ, Weigel BJ, Perentesis JP, Dusenbery KE, DeFor TE, Baker KS, Verneris MR. Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P = 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.
PMID: 16273111 [PubMed - indexed for MEDLINE]
4. Gynecol Oncol. 2006 Sep;102(3):583-6. Epub 2006 Apr 27.
Desmoplastic small round cell tumour: obstetric and gynecological presentations.
Church DN, Bailey J, Hughes J, Williams CJ. Department of Medical Oncology, Bristol Haematology and Oncology Centre, Horfield Road, Bristol, BS2 8ED, UK. email@example.com
BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare sarcoma primarily affecting young men. We report two cases in young women mimicking gynaecological malignancy. CASES: A 23-year-old woman underwent caesarean section for obstructed labour. At surgery, multiple tumour deposits were found throughout abdomen and pelvis. Histology and PCR confirmed DSRCT. Despite chemotherapy, the patient relapsed and died 27 months after diagnosis. A 29-year-old woman presented with abdominal distension and elevated Ca125. Imaging demonstrated widespread tumour within abdomen and pelvis. Histology confirmed DSRCT. Although attaining a complete response to chemotherapy, she relapsed within 2 months and died 11 months after diagnosis. CONCLUSION: DSRCT should be considered in the differential diagnosis of young women presenting with abdominal distension and multiple masses on imaging.
PMID: 16643996 [PubMed - indexed for MEDLINE]
5. Combined Transcriptional and Translational Targeting of EWS/FLI-1 in Ewing's Sarcoma
Silvia Mateo-Lozano, Prafulla C. Gokhale, Viatcheslav A. Soldatenkov, Anatoly Dritschilo, Oscar M. Tirado and Vicente Notario Authors' Affiliation: Laboratory of Experimental Carcinogenesis, Department of Radiation Medicine, V.T. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia
Requests for reprints: Vicente Notario, Department of Radiation Medicine, Georgetown University Medical Center, Room E215, Research Building, 3970 Reservoir Road NW, Washington, DC 20057-1482. Phone: 202-687-2102; Fax: 202-687-2221; E-mail: firstname.lastname@example.org.
Purpose: To show the efficacy of targeting EWS/FLI-1 expression with a combination of specific antisense oligonucleotides and rapamycin for the control of Ewing's sarcoma (EWS) cell proliferation in vitro and the treatment of mouse tumor xenografts in vivo.
Experimental Design: EWS cells were simultaneously exposed to EWS/FLI-1–specific antisense oligonucleotides and rapamycin for various time periods. After treatment, the following end points were monitored and evaluated: expression levels of the EWS/FLI-1 protein, cell proliferation, cell cycle distribution, apoptotic cell death, caspase activation, and tumor growth in EWS xenografts implanted in nude mice.
Results: Simultaneous exposure of EWS cells in culture to an EWS/FLI-1–targeted suppression therapy using specific antisense oligonucleotides and rapamycin resulted in the activation of a caspase-dependent apoptotic process that involved the restoration of the transforming growth factor-ß–induced proapoptotic pathway. In vivo, individual administration of either antisense oligonucleotides or rapamycin significantly delayed tumor development, and the combined treatment with antisense oligonucleotides and rapamycin caused a considerably stronger inhibition of tumor growth.
Conclusions: Concurrent administration of EWS/FLI-1 antisense oligonucleotides and rapamycin efficiently induced the apoptotic death of EWS cells in culture through a process involving transforming growth factor-ß. In vivo experiments conclusively showed that the combined treatment with antisense oligonucleotides and rapamycin caused a significant inhibition of tumor growth in mice. These results provide proof of principle for further exploration of the potential of this combined therapeutic modality as a novel strategy for the treatment of tumors of the Ewing's sarcoma family.
6. Phase-1 study of isophosphoramide mustard (IPM)-lysine in advanced cancers.
- Sub-category: Soft Tissue
- Category: Sarcoma
- Meeting: 2006 ASCO Annual Meeting
Abstract No: 9524
- Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 9524
Author(s): R. Gale, A. Van Vugt, L. Rosen, L. Chang, P. Lorusso, M. Valdivieso, L. Malburg, R. Struck, L. Morgan Abstract: Background: IPM is a bi-functional alkylator which cross-links DNA through G:C base-pairs resulting in irreparable 7-atom inter-strand cross-links. IPM is the active moiety of ifosfamide (IFOS), a pro-drug of IPM. IPM is active in diverse cancer models but is unstable. We stabilized IPM with lysine (IPM-lysine; ZIO-201). ZIO-201 was active in pre-clinical models including human cancer cell lines, human-mouse xenografts and cancers resistant to cyclophosphamide (CPA) and IFOS. Because ZIO-201 is not metabolized to acrolein or chloroacetaldehyde, bladder and CNS toxicities are unlikely. Methods: Phase-1 trial in subjects with advanced cancers. ZIO-201 was given daily for 3 consecutive d at a starting dose of 30 mg/me2/d every 3 w. Neither mesna nor IV hydration were given. 11 dose levels were studied in 18 subjects up to 795 mg/me2/d; dose-escalation continues. Data on the 1st 15 subjects are available for analysis. Results: Median age was 59 y (range, 18-70 y); 10 subjects were male. Diagnoses included colorectal cancer (N=5), sarcoma (N=3) and 1 subject each with gastric, lung, bladder, prostate, ovary and thyroid cancers and mesothelioma. 7 had extensive and 8, limited disease. All subjects received extensive prior therapy. Median N cycles was 2 (range, 1-13). Toxicities > grade-2 occurring in > 20% of subjects included anemia (N subjects=4) and diverse GI complaints (N=4). 4 of 8 subjects receiving doses > 445 mg/me2/d had transient proximal renal tubular acidosis. There was no hemorrhagic cystitis or CNS toxicity. 1 subject with mesothelioma had stable disease > 13 mo. Pharmacokinetic studies at 595 mg/me2/d showed a tmax = 13 min (SD ± 9 min), Cmax = 44.7 µg/mL (SD ± 34.1 µg/mL), t1/2 = 35 min (SD ± 7 min) and AUC0-∞ = 1.68 mg·min/ml (SD ± 1.26 mg·min/ml). Conclusions: These data suggest a possible role for ZIO-201 in IFOS-sensitive cancers (especially sarcoma and lymphoma). ZIO-201 may also be active in CPA and IFOS-resistant cancers. Comparable or greater efficacy with less toxicity is expected.
1. Results of multimodal treatment for desmoplastic small round cell tumors. - 2005 Jan;40(1):251-5.
Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are rare aggressive neoplasms that frequently present with large symptomatic intraabdominal masses. We examined the effects of multimodal therapy including induction chemotherapy, aggressive surgical debulking, and external beam radiotherapy on patients with DSRCT. METHODS: Institutional Review Board permission was obtained. Sixty-six patients were diagnosed by histology, immunohistochemistry, and or cytogenetics as having DSRCT at our institution from July 1, 1972, to July 1, 2003. Data were collected on patient demographics, presenting symptoms, tumor location and extent, treatment regimen, and overall survival. RESULTS: A majority of patients were male (91%), Caucasian (85%), and with a median age of 19 (7-58) years old at diagnosis. The most common presenting complaint was an intraabdominal mass (64%). In 63 patients (96%), the primary tumor was located in the abdomen or pelvis. Thirty-three (50%) had positive lymph nodes and 27 (41%) had distant parenchymal metastases at diagnosis. Overall, 3- and 5-year survivals were 44% and 15%, respectively. Twenty-nine of these patients (44%) underwent induction chemotherapy (P6), surgical debulking, and radiotherapy. Three-year survival was 55% in those receiving chemotherapy, surgery, and radiotherapy vs 27% when all 3 modalities were not used (P < .02). Gross tumor resection was highly significant in prolonging overall survival; 3-year survival was 58% in patients treated with gross tumor resection compared to no survivors past 3 years in the nonresection cohort (P < .00001). Ten patients (15%) have no evidence of disease with a median follow-up of 2.4 years (range, 0.4-11.2 years). CONCLUSIONS: Multimodal therapy results in improved survival in patients with DSRCT. Aggressive surgical resection of these extensive intraabdominal neoplasms correlates with improved patient outcome.
PMID: 15868593 [PubMed - indexed for MEDLINE]
2. Response to vinorelbine and low-dose cyclophosphamide chemotherapy in two patients with desmoplastic small round cell tumor Andrea Ferrari, MD 1 *, Federica Grosso, MD 2, Silvia Stacchiotti, MD 2, Cristina Meazza, MD 1, Elena Zaffignani, MD 1, Alfonso Marchianò, MD 3, Michela Casanova, MD 1 1Pediatric Oncology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy 2Adult Sarcoma Medical Oncology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy 3Radiology Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy
email: Andrea Ferrari (email@example.com)
- Correspondence to Andrea Ferrari, Pediatric Oncology Unit, Istituto Nazionale Tumori, Via G. Venezian, 1-20133 Milano MI, Italy.
Keywords desmoplastic small round cell tumor • low-dose cyclophosphamide • metronomic therapy • vinorelbine
We report two cases of abdominal desmoplastic small round cell tumor (DSRCT) that showed a clinical response to the vinorelbine/low-dose cyclophosphamide combination that has been claimed to be effective for rhabdomyosarcoma. This observation may prompt further investigation into the activity of such a regimen in DSRCT patients with recurrent or refractory disease, with a view to a possible future role as maintenance therapy in controlling minimal residual disease in patients who achieve complete remission with intensive induction multimodality therapy. Pediatr Blood Cancer © 2005 Wiley-Liss, Inc.
Received: 5 September 2005; Accepted: 5 October 2005
3. World Journal of Gastroentrology - Combined resection and multi-agent adjuvant chemotherapy for desmoplastic small round cell tumor arising in the abdominal cavity: Report of a case
Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.
Desmoplastic small round cell tumor (DSRCT) is a rare malignancy with highly aggressive behavior spreading widely along the serosal surface. Gerald and Rosai first described the disease in 1989 in terms of distinctive pathologic findings: a nesting pattern of cellular growth within dense desmoplastic stroma, and immunohistochemical co-expression of epithelial, muscle and neural markers[1-3]. A specific chromosome abnormality, t (11;22) (p13;q11 or q12) was identified, and DSRCT is believed to be the result of involvement of both Wilms’ tumor suppressor gene and Ewing’s sarcoma gene located on Chromosome 11 and 22, respectively. The tumors usually present in young male individual, as a single mass or multiple masses in the abdominal-pelvic cavity with metastases common to peritoneum, liver and lymphoid tissue. Some cases had presentation sites in the scrotum[6,7], pleural space[6,8,9] and mediastenum[6,10]. Complete resection is generally difficult to obtain due to multiple foci and dissemination. The standard treatment protocol has not been well established. Chemotherapy currently seems to be the best potential treatment. This work reports on a case of DSRCT with no disease for 20 months following complete resection of tumors and postoperative multi-agent adjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and PAVEP (cyclophosphamide, etoposide, doxorubicin and cisplatin).
The 27-year-old man had intermittent epigastralgia, abdominal fullness, and chronic constipation for 3 months. He presented sudden onset of hematemesis (500 mL) outside our hospital on September 15, 2003. Physical examination revealed only mild epigastric tenderness. The hemoglobin level was normal. Endoscopy showed esophageal and cardiac ulcers without complete study owing to poor compliance of the patient. Upper gastrointestinal (GI) series demonstrated a mass with external compression at the gastric antrum (Figure 1). Abdominal computed tomography (CT) indicated a 5 cm heterogeneous mass located among the gastric antrum, duodenum loop and pancreatic head (Figure 2). Barium enema study showed external compression of the middle transverse colon, ileocecal valve and ascending colon (Figure 3). Laparoscopic biopsy was performed because multiple intra-abdominal organs were involved. A histopathologic exam of the specimen revealed poorly differentiated carcinoma. The patient was then referred to our hospital for further treatment.
No significant medical or pertinent family history was found. Additionally, no history of exposure to carcinogens such as radiation, tobacco or asbestos was identified. Hematogram showed hemoglobin, 110 g/L and white blood cells (WBC), 11 × 109/L. Biochemistry studies yielded normal results. Tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9 were within the normal rage. Laparotomy was performed on October 3, 2003 to relieve the patient’s symptoms. During the operation, the gastric antrum, pancreas, terminal ileum and cecum, sigmoid colon, rectovesicular region and omentum were all involved by tumors. Right hydroureter was also identified due to external compression by the tumor. Subtotal gastrectomy, partial pancreatic resection, total omentectomy, proctocolectomy and J-pouch ileo-anal anastomosis were performed for complete resection of tumors. A double-J stenting was inserted through the ureterostomy by a urologist.
A histopathologic exam of the surgical specimens demonstrated invasive nests of poorly differentiated carcinoma, mainly involving omentum, pancreatic, and gastric, colonic and ileal muscular walls with focal mucosa extension. Large and small foci of tumor cells were observed in fibrous interstitium (Figure 4A). The tumor cells had a small spherical or spheroid nucleus, which was rich in chromatin (Figure 4B). One of 20 peri-colic lymph nodes was positive for metastasis. The section margins were free of tumor. The immunohistochemical tests were positive for desmin (Figure 4C), epithelium membrane antigen and neuron-specific enolase, and focal positive for vimentin, indicating DSRCT.
J-pouch ileo-anal anastomosis leakage with intra-abdominal abscess occurred on postoperative day 7. The patient recovered after treatment by antibiotics and CT-guidance drainage. Postoperative adjuvant chemotherapy with high dose 5-FU (2 600 mg/m2, day 1) was initiated on 24th October, 2003. The patient received altogether eight courses of chemotherapy of 5-FU thereafter. Another chemotherapeutic regimen consisting of PAVEP (cyclophosphamide 300 mg/m2, d 1-3; etoposide 75 mg/m2, day 1-3; doxorubicin 40 mg/m2, day 1; cisplatin 100 mg/m2, day 4) was administered on February 17, 2004. Neutropenic (WBC, 2×109 /L) fever developed one week later even though prophylactic granulocyte colony-stimulating factor (G-CSF) was given the day following chemotherapy. The patient received broad-spectrum antibiotics treatment, and his fever was gradually controlled. He was discharged 12 d later when his WBC returned to normal. Another four chemotherapy courses with PAVEP regimens were completed on May 24, 2004. He survived without any disease 20 mo after the surgery.
DSRCT has a strong male predominance, and the majority arises below the diaphragm with serosal spreading and easily metastasizing to lung, liver, and lymphoid tissues[2,6,11]. The most common site was the pelvis (62%), followed by spreading widely on the peritoneal surface (42%). Symptoms such as abdominal pain (52.1%), increased abdominal girth (8.4%), and abdominal mass (5.6%) have been reported. Patients also presented with GI or genitourinary obstruction. GI bleeding does not appear to have been reported in the literature. This patient was the first case with DSRCT presented with GI bleeding. The bleeding was associated with tumors directly invading to the gastric mucosa.
The prognosis of DSRCT is dismal with a mean survival of 1.5-2.5 years since the wide spread of the tumor makes radical resection difficult to achieve, and chemotherapeutic agents are only temporarily effective in treating this disease[6,12-15]. Farhat et al  recommended that PAVEP should be the first-line drug for treating DSRCT after reviewing 8 cases with complete remission from the treated 60 cases. However, grade four neutropenia occurred in 69% cycles while administering PAVEP regimens despite prophylactic use of G-CSF in 90% of cases in his report. Considering the severe and life-threatening side effects and uncertainty of therapeutic results of PAVEP regimens, other safer and effective chemotherapeutic agents should be considered prior to PAVEP.
5-FU is well-known as a chemotherapeutic agent and a radioactive sensitizer broadly used for GI tract cancers and disseminated intra-abdominal metastatic adenocarcinoma. Gerald et al  reported a successful application of 5-FU in treating intra-abdominal DSRCT. Kretschmar et al  also reported 60% responsive rate to this tumor. Since DSRCT is a highly aggressive and progressive malignancy, post-operative adjuvant chemotherapy should be initiated as soon as possible. Post-operative anastomotic leakage and right urinary tract obstruction arose in our case. Therefore, 5-FU was applied instead of PAVEP regimen as the first-line drug to treat DSRCT considering the infection problems and the adverse effects of PAVEP regimens such as myelo-suppression and renal toxicity.
DSRCT is a disease so rare that no consistent response to chemotherapy was seen in the literature review. Kurre et al  presented another alkylator-based chemotherapy protocol named P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, and etoposide), which only improved the progression-free survival without significant survival benefit. Gil et al  recommended performing perioperative intraperitoneal chemotherapy when treating DSRCT patients, but no evidence of prolonged survival was observed.
The effect of complete resection of disseminated tumors on survival is still unknown because of the rarity of achieving complete resection at operation. Gil et al  reported that the median survival was 20 mo in 4 patients with complete resection of tumors compared with 11 mo in 3 cases without complete resection. Significantly, long-term survivors, including one patient who survived for 101 mo, have been reported when utilizing combined modality treatment comprising surgery and multi-agent chemotherapy. The influence of other salvage therapies, such as immunotherapy or bone marrow ablation, is still undetermined. In this work, the patient underwent complete resection of tumors and received postoperative adjuvant chemotherapy surviving without any disease and without gastrointestinal symptoms 20 mo after surgery, similar to that in Gil’s report.
In conclusion, the optimal treatment for DSRCT remains to be determined, indicating the rarity and virulent behavior of the disease. In this advanced DSRCT patient, aggressive surgery combined with postoperative systemic multi-agent adjuvant chemotherapy was justified not only to relieve his symptoms but also to try to improve his outcome. The effectiveness and safety of chemotherapeutic regimens still need to be improved to treat this disease as early as possible postoperatively, especially when patients cannot tolerate the toxicity of alkylator agents after such an aggressive surgery.
4. Desmoplastic small round cell tumour (DSRCT) is a rare sarcoma primarily affecting young men. We report two cases of DSRCT in young women presenting as a gynaecological malignancy, in one case with obstructed labour.
A 23 year-old women underwent caesarean section for obstructed labour. At surgery multiple tumour deposits were found throughout the abdomen and pelvis. Histology demonstrated typical features of DSRCT and PCR confirmed the characteristic 11;22 translocation. Despite chemotherapy the patient relapsed and died 27 months after diagnosis. A 29 year-old woman presented with abdominal distension and elevated Ca-125. Imaging demonstrated widespread tumour within the abdomen and pelvis. Histology confirmed DSRCT. Although attaining a complete response to chemotherapy she relapsed within 2 months and died 11 months after diagnosis.
DSRCT should be considered in the differential diagnosis of young women presenting with abdominal distension and multiple masses on imaging.
Desmoplastic small round cell tumour (DSRCT) is a rare soft tissue sarcoma of the Ewing's family of tumours first described in 1987. It is characterised by a specific chromosomal translocation, t(11;22)(p13;q12) leading to the fusion of the WT1 and EWS genes .
The clinical pattern of disease is typically one of multiple intra-abdominal tumour deposits on serosal surfaces. prognosis is poor with median survival less than 30 months and few long-term survivors [2,3,4]. The tumour predominantly affects young adults (median age 19-25 years) and displays a striking male preponderance (82-95% of cases) [3,4].
DSRCT in females occurs at an earlier age than in males  and may present with abdominal distension, pelvic mass or elevated Ca125 . We report two cases of DSRCT in young women, one mimicking epithelial ovarian cancer, the other presenting with obstructed labour, the first such report of its kind.
In February 2003 a healthy 23 year-old pregnant woman was admitted to the obstetric department of another institution in labour. Pregnancy had been unremarkable. On vaginal examination firm nodules were noted in the posterior fornix. As progress of labour was unsatisfactory oxytocic augmentation was commenced. Despite this there was no further progress in labour beyond 5cm dilatation and a caesarean section was performed. At surgery the initial finding was of unexpected ascites. Further inspection revealed multiple large volume tumour deposits over the pelvic and abdominal peritoneum and an 8cm hard irregular pelvic mass obstructing labour.
Tumour biopsies were taken, but no attempt at debulking could be made. A healthy boy was delivered.
AE1/3 Positive EMA Negative S100 Negative Chromogranin Negative Synaptophysin Negative NSE Negative HCG Negative AFP Negative Inhibin Equivocal Desmin Positive WT-1 Positive CD99 Negative
Histopathology of biopsy material demonstrated sheets of poorly differentiated cells with little cytoplasm and high mitotic rate. Immunohistochemical features are shown in table 1 (right). PCR of tumour tissue demonstrated the EWS-WT1 fusion transcript . A diagnosis of DSRCT was made.
Staging CT confirmed widespread intra-peritoneal metastases and multiple cystic metastases within the liver (Fig 1a,1b). Bone marrow trephine revealed no evidence of tumour infiltration.
The patient was counselled about the rarity and poor prognosis associated with this tumour. In view of the parenchymal liver metastases aggressive debulking surgery was not performed. A major consideration in treatment planning was the need for the patient to spend time with her baby whilst receiving therapy. For this reason the dose intensive regimens  used in some centres for this disease were not considered appropriate.
An alternating regimen using standard doses of drugs effective in soft tissue sarcoma was chosen. This comprised cisplatin (100mg/m2 d1) and doxorubicin (25mg/m2 d1-3) alternating with TIP (paclitaxel 175mg/m2 d1, cisplatin 20mg/m2 d1-5 and ifosfamide 1g/m2 d1-5 with mesna uroprophylaxis). Six cycles of chemotherapy were given in total, ending in July 2003.
Initially the option of consolidation with high dose therapy with autologous stem-cell transplant was considered if complete or near complete response was attained with chemotherapy. However as repeat imaging during treatment demonstrated only modest tumour regression it was felt that high dose chemotherapy would not be beneficial. Restaging CT scan post-treatment (Fig 1c,1d) showed significant residual disease bulk. The potential role of aggressive debulking surgery in pelvis and liver was raised, but in view of the uncertain benefit of this approach, her lack of symptoms and good quality of life the patient declined.
The original pathology sample was tested for c-Kit (CD117) status as expression of the receptor has been noted in DSCRT  raising possibility of therapeutic response to imatinib. Unfortunately the tumour proved c-Kit negative on immunohistochemistry. A policy of close observation until disease progression was decided upon.
Over subsequent months continued disease regression was observed. The patient remained clinically well, and was able to care for her child. In June 2004 although the patient was asymptomatic, follow-up imaging demonstrated progressive disease within liver and around splenic hilum. This was not amenable to surgical debulking. In view of the lack of symptoms further treatment was not given.
However, in October 2004 symptomatic ascites developed, requiring paracentesis. A decision was made to commence further palliative chemotherapy using carboplatin (AUC 6 d1) and etoposide (150mg/m2 IV d1-3), 3 weekly cycles. Carboplatin was given at 80% dose in view of previous febrile neutropenia and high calculated creatinine clearance. Despite this the first cycle of treatment was complicated by febrile neutropenia and grade 4 thrombocytopenia. A further 20% reduction for both drugs was therefore made for subsequent cycles. A total of 6 cycles treatment were given until February 2005. The patient obtained significant palliation, not requiring further abdominal paracentesis whilst on treatment.
After some 6 weeks of symptomatic remission in April 2005 the patient developed further ascites and symptoms of gastric outflow obstruction. The clinical impression of progressive disease was confirmed on CT scan, which demonstrated significant increase in tumour bulk within the liver and multiple new peritoneal lesions. Unfortunately, the patient's clinical condition deteriorated rapidly, and despite further palliative chemotherapy with carboplatin (AUC 5) and gemcitabine (1000mg/m2 d1,d8) she died in May 2005, 27 months after initial diagnosis."
A 29 year-old woman presented in October 2004 with a two-week history of abdominal istension, discomfort and early satiety. She had no gynaecological, urinary or other gastrointestinal symptoms.
Clinical examination demonstrated ascites, confirmed on computerised tomography (CT), which also revealed a mass in the pelvic floor involving uterus, and numerous peritoneal deposits (fig 2a). Radiological appearance of liver and lungs was normal. Serum Ca125 at presentation measured 196 Kiu/l (range 0-20). Abdominal paracentesis yielded 4.5L of fluid, cytologic analysis of which demonstrated pleomorphic malignant cells. She was referred to the department of gynaecological oncology where diagnostic laparoscopy confirmed disseminated intra-abdominal malignancy, revealing tumour deposits on all peritoneal surfaces and adherent to bowel (Fig 3). Disease was not amenable to surgical debulking. Biopsies demonstrated poorly differentiated tumour with desmoplastic background stroma. Immunophenotyping showed cytoplasmic co-expression of cytokeratin with desmin with focal CD99 positivity.
Unfortunately sufficient material was not available for molecular analysis. A diagnosis of DSCRT was made.
She received chemotherapy using alternating BEP (cisplatin 50mg/m2 d1,2 etoposide 120mg/m2 d1-3, bleomycin 30,000IU d2,8,15, 3 weekly cycle) and TIP (Cisplatin 20mg/m2 d1-5, ifosfamide 1g/m2 d1-5, paclitaxel 175mg/m2 d1, 3 weekly cycle), beginning November 2004. Treatment was well tolerated.
Ascites, which prior to treatment required weekly drainage, did not recur after commencement of chemotherapy. CT scan after four cycles of treatment demonstrated complete tumour response (fig 2b). Serum Ca125 fell to 6Kiu/l. Six cycles of chemotherapy were given in total, completed in March 2005.
In May 2005, six weeks after cessation of chemotherapy a further CT was performed to confirm response. This demonstrated disease recrudescence, revealing omental and peritoneal deposits (fig 2c). As the patient was asymptomatic, and any further treatment was likely to be palliative a policy of close observation was decided upon.
However by July 2005 the patient developed symptomatic ascites. Further chemotherapy was commenced using CAP (cyclophosphamide 500mg/m2 d1, doxorubicin 50mg/m2 d1, cisplatin 50mg/m2 d1).
Unfortunately after the first cycle of treatment, the patient was admitted to hospital with increasing abdominal distension and symptoms of gastrointestinal obstruction. CT revealed significant increase in disease bulk and widespread dilatation of bowel. In view of the rapid deterioration and obstructive abdominal symptoms further chemotherapy was felt to be unlikely to be of benefit, and the patient was discharged home with palliative care support. She died in October 2005, less than 12 months after diagnosis.
Since its recognition as a distinct entity in 1987 the pathological and clinical characteristics of DSRCT have been well described in a number of publications. DSRCT is a disease predominantly affecting adolescents and young adults [3,4]. Over 80% of those affected are male [2,3,4]. Most tumours occur in the abdomen, although thoracic and paratesticular primary sites have been described. Patients typically present with pain, palpable mass, abdominal distension, ascites or symptoms related to obstruction of viscus [1,2]. At diagnosis patients commonly have multiple serosal tumour deposits within abdomen and pelvis . The most frequent sites of metastases are liver, lymph nodes, lung and bone marrow. CT is the radiological investigation of choice, and suspicion of DSRCT should be increased by imaging demonstrating multiple peritoneal soft tissue masses without obvious primary.
Laparoscopy can be used to confirm imaging findings and to provide sufficient biopsy material for molecular cytogenetics, an important element of the diagnosis. Histologically, DSRCT typically comprises nests of tumour cells surrounded by a dense desmoplastic stroma, with tumour cells coexpressing epithelial (cytokeratin, epithelial membrane antigen) mesenchymal (vimentin, desmin) and less frequently neural (neurone specific enolase) cell markers [3,8]. Confirmation of diagnosis of DSRCT can be made by demonstration of the characteristic chromosomal translocation t(11;22)(p13;q12), an event thought to be pivotal in the disease pathogenesis, resulting in fusion of the Ewing sarcoma gene (EWS) localised to 22q12, to the Wilms' tumour suppressor gene (WT1) localised to 11p13 [1,8].
The EWS gene encodes a 656 amino acid protein of unknown function, and is the gene most commonly involved in reciprocal sarcoma translocations. WT1 is a tumour suppressor gene expressed in the developing genitourinary tract and involved in development of a subset of Wilms tumours [1,8]. It encodes a transcription factor that acts as a transcriptional repressor in-vitro [1,8]. The chimeric protein produced by the t(11;22)(p13;q12) fuses the amino terminal of EWS with the DNA binding domain of WT1 and likely functions as a transcriptional activator,  inducing production of endogenous platelet-derived growth factor (PDGF) amongst other tumourigenic stimuli.
Treatments for DSRCT comprise chemotherapy, surgical resection and abdominal radiotherapy. An intensive alkylator-based chemotherapy regimen  appears to improve survival when compared with standard dose chemotherapy in retrospective series . This regimen causes significant toxicity and requires intensive transfusional and antibiotic support. Surgical resection of more than 90% of disease is also associated with better prognosis,  although whether optimum resection is the cause of improved survival or the consequence of a more favourable disease phenotype is unclear.
Whole abdominal radiotherapy in 1.5Gy fractions to a dose of 30Gy is recommended in some centres, although toxicity in the form of small bowel obstruction occurs in a third of patients. In a recent retrospective review of 66 patients treated at the Memorial Sloan Kettering Cancer Centre from 1972-2003 the use of multimodality treatment as detailed above was associated with a significant improvement in survival .
In spite of aggressive therapy the prognosis of DSRCT is extremely poor, with median survival of less than 30 months and only 44% and 15% of patients alive at 3 and 5 years respectively after diagnosis [2,3,4]. Patients with hepatic parenchymal metastases have a dismal prognosis, with median survival of 18 months and no long-term survivors in one series . Interestingly, our first patient survived 27 months from diagnosis, having had no surgery or radiotherapy and only standard dose chemotherapy, demonstrating the biological heterogeneity of the disease.
In spite of intensive efforts to improve outcomes in DSCRT through conventional therapies, breakthroughs in treatment are likely to be made through the use of novel treatment approaches. It is interesting to note that SU101, an inhibitor of the PDGF receptor pathway, produced rapid symptomatic improvement and prolonged disease stabilisation in a patient with refractory progressive DSRCT treated in a phase 1 trial . However a recent phase II trial of the tyrosine kinase inhibitor imatinib (Gleevec) in relapsed paediatric tumours produced no responses in patients with DSRCT .
An alternative treatment approach of interest is the use of immunotherapies against DSRCT cell surface antigens or fusion protein neoantigens. Clearly, intense research efforts are needed in order to improve outcomes in this disease.
This is the first reported case of DSRCT presenting with obstructed labour. Aside from its extreme rarity however this report, together with our second case illustrates the characteristic clinical picture and dismal prognosis associated with this tumour. Gynaecological oncologists should be mindful of the possibility of DSRCT in young women presenting with abdominopelvic symptoms and multiple peritoneal masses on imaging.
1. Gerald WL, Ladanyi M, de Alava E, Cuatrecasas M, Kushner BH, LaQuaglia MP, Rosai J. Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 1998;16(9):3028-36.
2. La Quaglia MP, Brennan MF. The clinical approach to desmoplastic small round cell tumor. Surg Oncol. 2000;9(2):77-81.
3. Ordonez NG. Desmoplastic small round cell tumor: I: a histopathologic study of 39 cases with emphasis on unusual histological patterns. Am J Surg Pathol 1998;22(11):1303-13.
4. Lal DR, Su WT, Wolden SL, Loh KC, Modak S, La Quaglia MP. Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg 2005;40(1):251-5.
5. Parker LP, Duong JL, Wharton JT, Malpica A, Silva EG, Deavers MT. Desmoplastic small round cell tumor: report of a case presenting as a primary ovarian neoplasm. Eur J Gynaecol Oncol. 2002;23(3):199-202.
6. Kushner BH, LaQuaglia MP, Wollner N, Meyers PA, Lindsley KL, Ghavimi F, Merchant TE, Boulad F, Cheung NK, Bonilla MA, Crouch G, Kelleher JF Jr, Steinherz PG, Gerald WL. Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol. 1996;14(5):1526-31.
7. Chow WA, Chu P, Doroshow JH. Proc Am Soc Clin Oncol 2003; 22 page 826, (abstr 3321)
8. Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors; desmoplastic small round-cell tumors. Cancer Genet Cytogenet 2002; 1;138(1):1-10.
9. Adamson PC, Blaney SM, Widemann BC, Kitchen B, Murphy RF, Hannah AL, Cropp GF, Patel M, Gillespie AF, Whitcomb PG, Balis FM. Pediatric phase I trial and pharmacokinetic study of the platelet-derived growth factor (PDGF) receptor pathway inhibitor SU101. Cancer Chemother Pharmacol 2004;53(6):482-8.
10. M. Bond, M. L. Bernstein, A. Pappo, K. R. Schultz, M. Krailo, M. Fouladi, D. A. Hill, M. Heinrich, S. Blaney, P. C. Adamson. Phase 2 trial of Imatinib mesylate (IM) for treatment of recurrent or refractory."
Gil A, Gomez Portilla A, Brun EA, Sugarbaker PH. Washington Cancer Institute, Washington, DC 20010, USA.
Rare diseases are often associated with uninformed medical decisions and poorly executed treatments because of inexperience of the physicians. Desmoplastic small round-cell tumor is a rare disease that is a form of peritoneal surface malignancy usually affecting young males, with a mean survival of 29 months. In order to begin to build a more knowledgeable clinical pathway all 7 patients treated at the Washington Hospital Center were studied and compared to patients described in the medical literature. Clinical and pathological data, tumor distribution, cytoreductive surgery, completeness of cytoreduction and survival were recorded and analyzed. The first most common symptoms were pain, increased abdominal girth and palpable abdominal mass in our patients and in the literature review. The overall survival did not improve with cytoreductive surgery plus intraperitoneal chemotherapy (mean survival 32 months); however, 2 long-term survivors who responded to systemic chemotherapy of 55 and 101 months were recorded. The latter may be the longest survivor reported in the literature. No consistent response to chemotherapy was observed in our patients or in any literature review. Complete surgical removal of this malignancy did not correlate with survival in our patients. The absence of improved survival of our aggressively treated patients as compared to the literature was thought to be a consequence of an advanced stage of the disease. A new comprehensive approach that uses complete clearing of cancer by surgery and perioperative systemic and perioperative intraperitoneal chemotherapy as early as is possible in the natural history of the disease emerged as goals for future management.
PMID: 15557784 [PubMed - indexed for MEDLINE]
Desmoplastic Small Round Cell Tumour: A Description of Two Cases and Review of the Literature Paolo Lippe (a), Rossana Berardi (b), Claudia Cappelletti (b), Cristian Massacesi (b), Rodolfo Mattioli (a), Luciano Latini (b), Riccardo Cellerino (b)
a: Medical Oncology Unit, Fano and b: Medical Oncology Department, University of Ancona, Ancona, Italy
Address of Corresponding Author
Oncology 2003;64:14-17 (DOI: 10.1159/000066514)
Background: Desmoplastic small round cell tumour (DSRCT) is a recently described neoplasm, typically occurring in adolescent and young males. It usually shows an aggressive behaviour, presents in the abdomen, often with diffuse peritoneal implants. It has been demonstrated to be a chemosensitive tumour, generally with short-lasting response and poor survival gain from systemic chemotherapy. The authors report two additional cases of DSRCT and review the available medical literature. Patients and Methods: Two young males with intra-abdominal DSRCT were treated with a first-line chemotherapy including carboplatin, doxorubicin and etoposide. Results: Both of the patients obtained a partial response after first-line chemotherapy. The first patient started, subsequently, CD34+ stem cell mobilisation with high-dose cyclophosphamide (7 g/m2) in order to perform high-dose chemotherapy, but CD34+ cell count was insufficient to practice leukapheresis; he died 34 months after the diagnosis because of progression of the disease. The second patient underwent cytoreductive surgery, but progressed 2 months later despite second-line treatment; he died 16 months after the diagnosis. Conclusion: This experience confirms that DSRCT may be considered a chemosensitive tumour, highly aggressive, with short-lasting response to chemotherapy. Anyway, the recent literature suggests that multidisciplinary treatment including chemotherapy, surgery and radiation might be the proper approach to this rare malignancy.
Copyright © 2003 S. Karger AG, Basel
Paolo Lippe, MD Medical Oncology Unit, S. Croce Hospital I-61032 Fano (Italy) Tel. +39 0721 882396 E-Mail firstname.lastname@example.org
Publication details Int J Radiat Oncol Biol Phys 2002; 1 (54): 170-6
Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor Goodman KA, Wolden SL, La Quaglia MP, Kushner BH
PURPOSE: Desmoplastic small round-cell tumor (DSRCT) is a rare, recently described intraperitoneal malignancy occurring predominantly in adolescent boys. Our objective was to evaluate the feasibility and outcome of whole abdominopelvic irradiation (WAPI) as part of a combined modality protocol for patients with DSRCT. METHODS AND MATERIALS: The records of all 21 patients treated with WAPI for DSRCT at our institution from 1992 to 2001 were retrospectively reviewed. Patients were treated on an institutional protocol with 7 cycles of an alkylator-based chemotherapy. After maximal surgical debulking, patients were treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 30 Gy. RESULTS: All 21 patients completed the prescribed treatment. The median follow-up was 28 months. The overall survival and relapse-free survival rate at 3 years was 48% and 19%, respectively. The median survival was 32 months, and the median time to relapse was 19 months. Most relapses were intraperitoneal and/or hepatic. Acute toxicities included Radiation Therapy Oncology Group Grade 2 upper and lower gastrointestinal toxicity in 81% and 71% of patients, respectively. All patients experienced acute hematologic toxicity, with Grade 4 thrombocytopenia, leukopenia, and anemia in 76%, 29%, and 33%, respectively. The major long-term toxicity was small bowel obstruction, which occurred in 7 patients (33%) after surgery and WAPI. CONCLUSION: DSRCT is a rare and highly lethal disease, requiring aggressive multimodality therapy. WAPI is feasible in conjunction with intensive chemotherapy and surgery. Hematologic and gastrointestinal toxicities are expected but manageable with diligent supportive care. The long-term efficacy of this therapy remains disappointing, thus novel approaches are being investigated.
- Citation: Proc Am Soc Clin Oncol 20: 2001 (abstr 1516)
Author(s): Brenda Weigel, Jennifer Hirshfeld, Robert Ettinger, Thomas Loew, Joseph Neglia, John Perentesis, University of Minnesota, Minneapolis, MN; Gunderson Lutheran Medical Center, LaCrosse, WI; University of Iowa, Iowa City, IA.
- Abstract: Desmoplastic Small Round Cell Tumor (DSRCT), first reported in 1989, is an aggressive tumor in the Ewing's sarcoma family of tumors most often occurring in young males. It typically presents with widespread intraabdominal seeding, metastasizes to liver and lymph nodes and is associated with a dismal prognosis. We report 6 patients (5 males, 1 female) with DSRCT diagnosed at a median age of 14.3 years (range 8-30 years). Tumor cytogenetic analysis was performed on 4 patients, 2 had the characteristic t(11,22) translocation and 1 had a t(8,10)del(22)(q11). All patients received induction therapy with intensive alkylating agent/anthracycline based regimens: vincristine, doxorubicin and cyclophosphamide (VAdriaC) alternating with ifosfamide, carboplatin and etoposide (3 patients); VAdriaC alternating with ifosfamide and etoposide (2 patients); or VAdriaC + methotrexate alternating with cisplatin, bleomycin and vinblastine (1 patient). Following induction chemotherapy, 2 patients had major responses and underwent debulking surgery; 2 patients had stable disease (SD) but were not candidates for surgery, and 2 patients had progressive disease (PD) and died from disease after failing salvage therapies. The 2 patients with SD were additionally treated with irinotecan which resulted in a PR in 1 patient, permitting surgery; and SD for 8 months in the other patient. Intensification therapy with high dose alkylators (busulfan/melphalan/thiotepa) and autologous stem cell transplant (ASCT) was conducted in all 3 patients that underwent surgical resection of their tumor. After recovery from ASCT, patients received whole abdominal irradiation therapy (XRT). A second stem cell re-infusion was performed in 1 patient following XRT. The 3 patients who underwent ASCT/XRT are alive, without evidence of disease 1 - 45 months post ASCT (12-53 months post diagnosis). No toxic deaths occurred. DSRCT is an aggressive malignancy, though intensive treatment with sarcoma-based chemotherapy, surgery, ASCT, and whole abdominal irradiation is feasible and may provide the possibility of successful therapy.
The clinical approach to desmoplastic small round cell tumor.
Quaglia MP, Brennan MF. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. email@example.com
Background and Objectives: Desmoplastic small round cell tumor (DSRCT) is an increasingly recognized entity with a historically poor prognosis. This article describes the present clinical management of these patients. Methods: We retrospectively reviewed our experience with 40 histologically proven cases of desmoplastic small round cell tumor diagnosed between 7/1/72 and 10/1/99. Thirty-five of these patients are the subjects of a previous report. Demographic data, mode of presentation, completeness of resection, and overall survival were assessed. Results: The overall survival from DSRCT remains very poor and in our series was 29% at three years from diagnosis. There is a significant correlation between use of intense alkylator therapy (P6 protocol), and gross total resection with improved overall survival. It is often technically feasible to remove large peritoneal masses using a tangential dissection technique. Extensive hepatic parenchymal or hilar involvement or extensive infiltration of the diaphragm in the region of the septum transversum and hepatic veins usually makes gross total resection impossible with a corresponding worsened prognosis. Conclusion: We recommend induction chemotherapy (P6) followed by aggressive surgical debulking and external beam radiotherapy for the treatment of DSRCT. Further progress will require new forms of treatment.
PMID: 11094327 [PubMed - indexed for MEDLINE]
1996 May;14(5):1526-31. Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.
Kushner BH, LaQuaglia MP, Wollner N, Meyers PA, Lindsley KL, Ghavimi F, Merchant TE, Boulad F, Cheung NK, Bonilla MA, Crouch G, Kelleher JF Jr, Steinherz PG, Gerald WL. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.
PMID: 8622067 [PubMed - indexed for MEDLINE]