פרופסור עפר מרימסקי
מומחה באונקולוגיה קלינית וקרינתית
Русский
English
מאמרים מדעיים בתחום סרקומה
Scientific Articles on SARCOMA
1. World J Surg. 2015 Aug;39(8):1895-901. doi: 10.1007/s00268-015-3038-0.
Visceral Fat Content Correlates with Retroperitoneal Soft Tissue Sarcoma (STS)
Local Recurrence and Survival.
Papoulas M(1), Weiser R, Rosen G, Gerstenhaber F, Merimsky O, Lubezky N, Klausner
JM, Lahat G.
Author information:
(1)Department of Surgery, The Sourasky Medical Center, Sackler School of
Medicine, Tel-Aviv University, 6 Weitzman St., Tel-Aviv, Israel,
BACKGROUND: Our aim was to evaluate the association between visceral fat content
with soft tissue sarcoma (STS) local recurrence and survival.
METHODS: One hundred and one computed tomography imaging studies of primary STS
patients who had complete macroscopic resection at our institution between 2002
and 2012 were reviewed, and retroperitoneal and circumferential fat contents were
measured. Correlations between imaging findings and clinical data were analyzed.
RESULTS: Fifty-seven STS tumors (56.4 %) were retroperitoneal; of them, 65 % were
high grade, median size was 15 cm (range 3-49), and the most common histological
subtype was high grade liposarcoma (31.6 %). Median follow-up length for the
entire cohort was 64 months (range 6-95). High visceral fat (VF) content ≥15
versus <15 mm was identified as a risk factor for retroperitoneal STS local
recurrence; 65.1 versus 26.7 %, respectively (p = 0.04); VF content did not
correlate with distant metastasis. Median overall survival (OS) length of
patients with VF ≥15 versus <15 mm was 57 months (range 2-144) versus not
reached, respectively (p = 0.007). Multivariable analysis identified VF ≥15 mm as
an independent risk factor for decreased OS (HR: 4.2, 95 % CI 1.07-16.67). In
contrast, circumferential fat content did not correlate with retroperitoneal STS
patient outcomes.
CONCLUSION: High VF content is an independent adverse prognosticator associated
with significantly higher rates of retroperitoneal STS local recurrence and
decreased patients survival. Local tumor biology may be affected by the presence
of adipose cells. Further clinical and molecular research is needed to establish
this premise.
PMID: 25804549 [PubMed - in process]
2. Ann Oncol. 2014 Sep;25 Suppl 3:iii21-6. doi: 10.1093/annonc/mdu255.
Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up.
ESMO/European Sarcoma Network Working Group.
Collaborators: Casali PG, Blay JY, Bertuzzi A, Bielack S, Bjerkehagen B, Bonvalot
S, Boukovinas I, Bruzzi P, Dei Tos AP, Dileo P, Eriksson M, Fedenko A, Ferrari A,
Ferrari S, Gelderblom H, Grimer R, Gronchi A, Haas R, Hall KS, Hohenberger P,
Issels R, Joensuu H, Judson I, Le Cesne A, Litière S, Martin-Broto J, Merimsky O,
Montemurro M, Morosi C, Picci P, Ray-Coquard I, Reichardt P, Rutkowski P,
Schlemmer M, Stacchiotti S, Torri V, Trama A, Van Coevorden F, Van der Graaf W,
Vanel D, Wardelmann E.
PMID: 25210085 [PubMed - indexed for MEDLINE]
3. Ann Oncol. 2014 Sep;25 Suppl 3:iii113-23. doi: 10.1093/annonc/mdu256.
Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and
follow-up.
ESMO/European Sarcoma Network Working Group.
Collaborators: Casali PG, Blay JY, Bertuzzi A, Bielack S, Bjerkehagen B, Bonvalot
S, Boukovinas I, Bruzzi P, Dei Tos AP, Dileo P, Eriksson M, Fedenko A, Ferrari A,
Ferrari S, Gelderblom H, Grimer R, Gronchi A, Haas R, Hall KS, Hohenberger P,
Issels R, Joensuu H, Judson I, Le Cesne A, Litière S, Martin-Broto J, Merimsky O,
Montemurro M, Morosi C, Picci P, Ray-Coquard I, Reichardt P, Rutkowski P,
Schlemmer M, Stacchiotti S, Torri V, Trama A, Van Coevorden F, Van der Graaf W,
Vanel D, Wardelmann E, Bolle S, Capanna R, Delaney T, Doglietto F, Fossati P,
Jeys L, Kasper B, Leithner A, Radaelli S, Scheipl S, Tamborini E, Uhl M,
Vleggert-Lankamp CL.
PMID: 25210081 [PubMed - indexed for MEDLINE]
4. Ann Oncol. 2014 Sep;25 Suppl 3:iii102-12. doi: 10.1093/annonc/mdu254.
Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up.
ESMO/European Sarcoma Network Working Group.
Collaborators: Casali PG, Blay JY, Bertuzzi A, Bielack S, Bjerkehagen B, Bonvalot
S, Boukovinas I, Bruzzi P, Dei Tos AP, Dileo P, Eriksson M, Fedenko A, Ferrari A,
Ferrari S, Gelderblom H, Grimer R, Gronchi A, Haas R, Hall KS, Hohenberger P,
Issels R, Joensuu H, Judson I, Le Cesne A, Litière S, Martin-Broto J, Merimsky O,
Montemurro M, Morosi C, Picci P, Ray-Coquard I, Reichardt P, Rutkowski P,
Schlemmer M, Stacchiotti S, Torri V, Trama A, Van Coevorden F, Van der Graaf W,
Vanel D, Wardelmann E, Colombo C, Fiore M, Mariani L, Miceli R, Pollock RE, Raut
CP, Strauss D, Swallow CJ.
PMID: 25210080 [PubMed - indexed for MEDLINE]
5. Am J Clin Oncol. 2014 Jul 17. [Epub ahead of print]
Single-institution Experience of SBRT for Lung Metastases in Sarcoma Patients.
Soyfer V(1), Corn BW, Shtraus N, Honig N, Meir Y, Kollender J, Merimsky O.
Author information:
(1)Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.
OBJECTIVES:: Lung metastasectomy is regarded as the standard procedure for
improving the prognosis of patients with metastatic sarcoma. Few reports are
available in the literature describing the value of stereotactic body radiation
therapy (SBRT) of lung metastases from primary sarcoma as an alternative to
surgical treatment. We therefore sought to expand the evidence base for this
modality.
MATERIALS AND METHODS:: Twenty-two patients with metastatic sarcoma to lung were
treated by SBRT. The retrospective analysis of overall survival, toxicity, and
local control of 53 treated lesions is presented in the study. Lung lesions were
grouped into 2 categories for follow-up: <10 mm or ≥10 mm diameter.
RESULTS:: Of 34 lesions <10 mm, 24 achieved complete response, 3 partial
response, and 7 stable disease. The results of 18 lesions measuring >10 mm were
as follows: 5 complete response, 5 progressive disease, and 8 stable disease. No
progressive disease of all SBRT treated lesions was found at a median follow-up
of 95 months (SD 32). Five-year overall survival of the entire group was 62% from
the time of diagnosis and 50% from start of treatment. The treatment was well
tolerated with minimal, mainly skin toxicity.
CONCLUSION:: SBRT is an effective tool that might be used as an alternative to
operative treatment of lung metastases in sarcoma patients.
PMID: 25036473 [PubMed - as supplied by publisher]
6. Med Oncol. 2014 May;31(5):936. doi: 10.1007/s12032-014-0936-1. Epub 2014 Apr 10.
Is it important to maintain high-dose intensity chemotherapy in the treatment of
adults with osteosarcoma?
Kushnir I(1), Kolander Y, Bickels J, Gortzak Y, Flusser G, Issakov J, Merimsky O.
Author information:
(1)Division of Oncology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel
Aviv, Israel.
Neoadjuvant chemotherapy for osteosarcoma is the standard of care, but there is
still confusion regarding the best chemotherapy regimen and the optimal
intensity. This retrospective study intends to evaluate whether there is a clear
correlation between the chemotherapy dose intensity (DI) and the percentage of
tumor necrosis, the risk of tumor recurrence after surgery and patient survival.
The medical records of all adult patients with localized osteosarcoma that
received treatment between the years of 1998 and 2009 at the Tel Aviv Sourasky
Medical Center were analyzed. We used multiple logistic/linear regression models
to test the effect of the neoadjuvant chemotherapy relative DI (RDI) on
histological response, recurrence and time to recurrence. A Cox regression
analysis was conducted for the effects of neoadjuvant chemotherapy RDI,
histological response, tumor location, gender and age on patient survival. Thirty
medical records were analyzed. Survival, histological response, recurrence and
time to recurrence were not affected by the chemotherapy RDI. The 5-year overall
survival of the patient's population was found to be 63% with a median survival
of 9.4 years. Patients with a good histological response had a longer survival
than those with a bad response (mean survival times 11.0 vs. 6.6 years, log-rank
test, P = 0.046). High DI is not a prognostic factor in osteosarcoma and
maintaining it should not be a prime priority. Histological response is a
prognostic but possibly not a reliable predictive factor, and further research is
needed in order to find other reliable factors.
PMID: 24719037 [PubMed - indexed for MEDLINE]
7. Expert Rev Anticancer Ther. 2014 Jun;14(6):705-10. doi:
10.1586/14737140.2014.895667. Epub 2014 Mar 10.
Optimal management of sarcomas of the breast: an update.
Nizri E(1), Merimsky O, Lahat G.
Author information:
(1)The Department of General Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv,
Israel.
Breast sarcomas are rare mesenchymal-derived breast tumors. The small number of
patients, the different histological subtypes, and the variation in clinical
practice impairs the ability to draw firm practice recommendations. Patient
management is often extrapolated from other soft tissue sarcomas, mostly of the
extremities in which more clinical data is available. Surgical resection with
negative margins is the goal of treatment, irrespective of the surgical
procedure; the implication of radiation and chemotherapy is variable. Further
advances in treatment should follow the assembly of breast sarcoma patients in
specific cancer networks in specialized sarcoma referral centers. The
characterization of molecular pathways active in tumorogenesis of these tumors
may pave the way for the application of novel therapeutic agents.
PMID: 24611696 [PubMed - indexed for MEDLINE]
8. Br J Radiol. 2013 Aug;86(1028):20130258. doi: 10.1259/bjr.20130258. Epub 2013 May
24.
Hypofractionated adjuvant radiation therapy of soft-tissue sarcoma achieves
excellent results in elderly patients.
Soyfer V(1), Corn BW, Kollender Y, Issakov J, Dadia S, Flusser G, Bickels J,
Meller I, Merimsky O.
Author information:
(1)Department of Oncology, Tel Aviv Sourasky Medical Center, Ashdod, Israel.
OBJECTIVE: Adjuvant radiation therapy (RT) is an essential part of combined
limb-sparing treatment of soft-tissue sarcoma (STS). Elderly or medically unfit
patients often have difficulty in completing 6-7 weeks of standard fractionated
daily treatment. Our aim was to evaluate the efficacy of a hypofractionated
adjuvant approach with RT for STS in elderly and debilitated patients.
METHODS: 21 elderly patients were treated with a short course of adjuvant RT
(39-48 Gy, 3 Gy per fraction) for STS. The medical records of the patients were
retrospectively reviewed for local or distant recurrence and side effects of RT.
RESULTS: At a mean 26 months of follow-up, three local recurrences (14%) were
detected. Eight patients (38%) had lung metastases during the observed period.
Three of them died from metastatic disease. The hypofractionated radiation was
well tolerated with minimum long-term side effects.
CONCLUSION: Hypofractionated adjuvant radiation appears to be an effective
treatment in terms of local control in elderly and debilitated patients.
ADVANCES IN KNOWLEDGE: The results of this study might provide an alternative to
commonly used standard fractionation of radiotherapy in sarcoma patients.
PMCID: PMC3745062
PMID: 23709514 [PubMed - indexed for MEDLINE]
9. Ann Oncol. 2012 Oct;23 Suppl 7:vii92-9.
Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up.
ESMO / European Sarcoma Network Working Group.
Collaborators: Blay JY, Blomqvist C, Bonvalot S, Boukovinas I, Casali PG, De
Alava E, Dei Tos AP, Dirksen U, Duffaud F, Eriksson M, Fedenko A, Ferrari A,
Ferrari S, del Muro XG, Gelderblom H, Grimer R, Gronchi A, Hall KS, Hassan B,
Hogendoorn P, Hohenberger P, Issels R, Joensuu H, Jost L, Jurgens H, Kager L, Le
Cesne A, Leyvraz S, Martin J, Merimsky O, Nishida T, Picci P, Reichardt P,
Rutkowski P, Schlemmer M, Sleijfer S, Stacchiotti S, Taminiau A, Wardelmann E.
PMID: 22997462 [PubMed - indexed for MEDLINE]
10. Ann Oncol. 2012 Oct;23 Suppl 7:vii49-55.
Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up.
ESMO / European Sarcoma Network Working Group.
Collaborators: Blay JY, Blomqvist C, Bonvalot S, Boukovinas I, Casali PG, De
Alava E, Dei Tos AP, Dirksen U, Duffaud F, Eriksson M, Fedenko A, Ferrari A,
Ferrari S, del Muro XG, Gelderblom H, Grimer R, Gronchi A, Hall KS, Hassan B,
Hogendoorn P, Hohenberger P, Issels R, Joensuu H, Jost L, Jurgens H, Kager L, Le
Cesne A, Leyvraz S, Martin J, Merimsky O, Nishida T, Picci P, Reichardt P,
Rutkowski P, Schlemmer M, Sleijfer S, Stacchiotti S, Taminiau A, Wardelmann E.
PMID: 22997454 [PubMed - indexed for MEDLINE]
11. Ann Oncol. 2012 Oct;23 Suppl 7:vii100-9.
Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and
follow-up.
ESMO / European Sarcoma Network Working Group.
Collaborators: Blay JY, Blomqvist C, Bonvalot S, Boukovinas I, Casali PG, De
Alava E, Dei Tos AP, Dirksen U, Duffaud F, Eriksson M, Fedenko A, Ferrari A,
Ferrari S, del Muro XG, Gelderblom H, Grimer R, Gronchi A, Hall KS, Hassan B,
Hogendoorn P, Hohenberger P, Issels R, Joensuu H, Jost L, Jurgens H, Kager L, Le
Cesne A, Leyvraz S, Martin J, Merimsky O, Nishida T, Picci P, Reichardt P,
Rutkowski P, Schlemmer M, Sleijfer S, Stacchiotti S, Taminiau A.
PMID: 22997441 [PubMed - indexed for MEDLINE]
12. Cancer Chemother Pharmacol. 2012 Dec;70(6):855-60. doi:
10.1007/s00280-012-1968-x. Epub 2012 Sep 28.
Clinical activity of mTOR inhibition in combination with cyclophosphamide in the
treatment of recurrent unresectable chondrosarcomas.
Bernstein-Molho R(1), Kollender Y, Issakov J, Bickels J, Dadia S, Flusser G,
Meller I, Sagi-Eisenberg R, Merimsky O.
Author information:
(1)The Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv
Sourasky Medical Center, Affiliated with the Sackler School of Medicine, Tel-Aviv
University, Israel.
OBJECTIVE: Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas,
poorly responsive to chemotherapy or radiotherapy. When local therapies in
recurrent or metastatic disease are exhausted, chemotherapy plays a marginal
role. Different molecular pathways have been shown to be activated in CS. In this
retrospective study, we summarize our experience in treating a cohort of patients
with recurrent unresectable CS with a combination of sirolimus (SIR) and
cyclophosphamide (CTX).
PATIENTS AND METHODS: Ten consecutive patients with unresectable CS were offered
off-label treatment with SIR and CTX between 2007 and 2012. Tumor response,
progression-free survival (PFS), adverse events, and other relevant clinical data
were analyzed.
RESULTS: The median patients' age was 49 (range 28-68). Median disease-free
interval since the primary diagnosis was 22.5 months. Median time from the
disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to
additional local surgical treatments, excision of metastases, or slow
asymptomatic progression. One (10 %) objective response was observed, and six (60
%) patients had stabilization of disease for at least 6 months. Three patients
had progressive disease. Median PFS was 13.4 months (range 3-30.3). No
significant adverse events were observed.
CONCLUSIONS: Although advanced CS remains an incurable disease, our experience
suggests that a combination of SIR and CTX is well tolerated and may have
meaningful clinical activity with disease control rate of 70 %. Further
prospective studies are warranted.
PMID: 23053256 [PubMed - indexed for MEDLINE]
13. Sarcoma. 2010;2010:927972. doi: 10.1155/2010/927972. Epub 2010 Mar 8.
Radiation therapy for palliation of sarcoma metastases: a unique and uniform
hypofractionation experience.
Soyfer V(1), Corn BW, Kollender Y, Tempelhoff H, Meller I, Merimsky O.
Author information:
(1)Division of Oncology, Institute of Radiation Therapy, Tel-Aviv Sourasky
Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel.
Radiotherapy (RT) is our preferred modality for local palliation of metastatic
soft tissue sarcoma (STS). A short and intense course of RT is usually needed for
rapid palliation and local control of metastatic disease. Seventeen patients at a
median age of 61 had symptomatic metastatic sarcoma and required rapid
palliation. The symptoms related to the metastases were either pain or
discomfort. All patients were treated by a short and intensive course of
administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week.
Median follow-up period was 25 weeks. The treatment was well tolerated. Acute
side effects included grade one skin toxicity. No wound complications were noted
among those undergoing surgery. Late side effects included skin pigmentation and
induration of irradiated soft tissues. Durable pain control was achieved in 12
out 15 cases treated for gross metastases. Tumor progression was seen in the 3
other cases within a period of two to nine months. Among 5 lesions which were
irradiated as an adjunctive treatment following resection, no local recurrence
was observed. The results of this series, although limited in size, point to the
safety and feasibility of hypofractionated RT for palliation of musculoskeletal
metastases from sarcoma.
PMCID: PMC2834957
PMID: 20224682 [PubMed]
14. Int J Gynecol Cancer. 2010 Feb;20(2):255-60. doi: 10.1111/IGC.0b013e3181c9e289.
Metastatic uterine leiomyosarcomas: a single-institution experience.
Bernstein-Molho R(1), Grisaro D, Soyfer V, Safra T, Merimsky O.
Author information:
(1)Division of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
BACKGROUND: Uterine leiomyosarcoma (LMS) is a rare disease and, when it recurs or
metastasizes, can rarely be cured. In a retrospective study, we summarized our
experience in treating a large cohort of patients with metastatic uterine LMS.
MATERIALS AND METHODS: Cases of recurrent or metastatic uterine LMS diagnosed
between 2000 and 2008 were analyzed. Survival was determined from the time of
initial diagnosis to last follow-up.
RESULTS: Thirty-three patients (median age, 55 years) were identified. Eighteen
patients were initially diagnosed with localized disease. Median disease-free
interval was 5.25 months, and overall survival (OS) is 43.7 months. Median OS of
15 patients with initially discovered metastatic disease is 31.4 months.
Different chemotherapy regimens produced approximately 30% response rates. Twelve
patients underwent at least 1 surgical resection of pulmonary or extrapulmonary
metastases. In this group, median progression-free survival was 7.9 months
(range, 0-33.9 months), median OS was 45.2 months (range, >8.1-78.8 months),
2-year survival rate was 83%, and 4-year survival rate was 25%.
CONCLUSIONS: Very few patients with recurrent or metastatic uterine LMS can be
curatively treated. Our experience suggests that modern multimodal therapy or
combining chemotherapy with aggressive surgery in selected patients may be
significant in prolonging survival of women with this fatal disease.
PMID: 20134269 [PubMed - indexed for MEDLINE]
15. J Neurooncol. 2009 Sep;94(3):383-8. doi: 10.1007/s11060-009-9862-z. Epub 2009 Mar
28.
Expression and significance of EGFR in malignant peripheral nerve sheath tumor.
Keizman D(1), Issakov J, Meller I, Maimon N, Ish-Shalom M, Sher O, Merimsky O.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel Aviv Sourasky
Medical Center (TASMC), Affiliated with Sackler School of Medicine, Tel-Aviv
University, Tel Aviv, Israel.
Erratum in
J Neurooncol. 2009 Sep;94(3):389. Meimon, Natalie [corrected to Maimon, Natalie].
Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma.
Epidermal growth factor receptor (EGFR) may play a putative role in its
pathogenesis, and be targeted for therapeutic purposes. The study was aimed at
investigating the expression and prognostic influence of EGFR in MPNST. Primary
and metastatic MPNSTs were immunostained with antibodies to EGFR. The total EGFR
expression (membranous and cytoplasmic) was analyzed by morphometry, grade of
positivity and the intensity (score 0-3). An EGFR composite score (range 0-300)
was calculated by multiplying the intensity by the grade. A composite score >10
was considered as EGFR overexpression. Score was correlated with clinical
behavior. Forty-three percentage of 46 patients with MPNST overexpressed EGFR in
the primary tumor, and had a higher prevalence of advanced-stage tumors (>or=IIc,
46% vs. 80%, P = 0.011). Patients without overexpression had a higher prevalence
of tumors with a low mitotic rate (31% vs. 0%, P = 0.049). Neurofibromatosis was
more prevalent in patients with EGFR overexpression (75% vs. 42%, P = 0.007).
Five year disease free survival (mean 30.1 vs. 17.4 months, P = 0.048), time to
progression (mean 9.2 vs. 5.2 months, P = 0.005) and 5 year survival (52% vs.
25%, P = 0.041, mean 54 vs. 43 months) were significantly higher among patients
without overexpression. EGFR appeared to play a role in MPNST progression. EGFR
overexpression was correlated with worse prognostic variables and course.
Clinical trials of targeting EGFR in MPNST are warranted.
PMID: 19330289 [PubMed - indexed for MEDLINE]
16. Am J Clin Oncol. 2009 Feb;32(1):34-7. doi: 10.1097/COC.0b013e31817b6087.
The co-occurrence of breast cancer and soft tissue sarcoma in a single cohort
series.
Geva R(1), Jiveliouk I, Inbar M, Meller I, Friedman E, Merimsky O.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky
Medical Center, Tel-Aviv, Israel.
BACKGROUND: The incidence of breast cancer (BC) and soft tissue sarcoma (STS) in
the Israeli general population is 97/10 women and 1.5/10 persons. It is expected
that 1.5/10 x 49/10 of the women in the general population will have both BC and
STS.
METHODS: A retrospective search of 1350 adult STS patient files that were
recorded between 1995 and 2005.
RESULTS: One hundred thirty-four patients with STS had multiple primary
malignancies. BC was observed in 27/64 patients (42%) before/after the STS:
BC-first in 19/27, BC-later in 8/27. Of 19 with BC-first the STS was related to
radiotherapy in 2, and to lymphedema in 1. Of 8 STS-first, only 1 got
chemotherapy before BC. Median interval between first to second malignancies was
6.9 years for BC-first, and 3.8 for BC-later. The incidence of BC among all
patients with STS-first followed by a second malignancy is 8/58 (14%), or 27/890
(3%) of all women STS-patients in the registry. The incidence of STS among the BC
patients was low, and most of our cases were therapy unrelated. Median survival
for BC-first was 305 months, versus 213 for STS-first.
CONCLUSIONS: BC and STS may naturally occur in the same individual. The etiology
for this phenomenon is unclear. Practically, BC screening in patients with STS is
warranted.
PMID: 19194122 [PubMed - indexed for MEDLINE]
17. Anticancer Drugs. 2008 Nov;19(10):1019-21. doi: 10.1097/CAD.0b013e328312c0e5.
Targeting the mammalian target of rapamycin in myxoid chondrosarcoma.
Merimsky O(1), Bernstein-Molho R, Sagi-Eisenberg R.
Author information:
(1)Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv
University, Tel-Aviv, Israel. merimsky@zahav.net.il
Myxoid chondrosarcoma is a slow-growing sarcoma poorly responsive to chemotherapy
and radiation therapy. Translational research has validated several proteins as
optional therapeutic targets. Significant responses are, however, rare. In this
paper we report an extraordinary response of myxoid chondrosarcoma to targeted
therapy by rapamycin in combination with cyclophosphamide. Our case points to a
possible novel therapeutic approach towards myxoid chondrosarcoma, by targeting
the mammalian target of rapamycin protein, and probably protein kinase C-alpha,
mitogen-activated protein kinase, and Jun N-terminal kinase too, by rapamycin.
PMID: 18827568 [PubMed - indexed for MEDLINE]
18. Sarcoma. 2000;4(1-2):7-10. doi: 10.1155/S1357714X00000025.
Gemcitabine in bone sarcoma resistant to Doxorubicin-based chemotherapy.
Merimsky O(1), Meller I, Kollender Y, Issakov J, Flusser G, Inbar M.
Author information:
(1)Department of Oncology The Tel-Aviv Sourasky Medical Center Affiliated with
Sackler Faculty of Medicine Tel-Aviv University Tel-Aviv Israel.
SUBJECTS AND METHODS: Seven patients with progressive localized or metastatic
chemo-resistant osteosarcoma were treated by gemcitabine.The protocol included
gemcitabine 1000 mg/m2/w for 7 consecutive weeks, followed by 1 week rest. If no
progression was observed,maintenance by gemcitabine 1000 mg/m2/w for 3 weeks
every 28 days was given until failure was clinically or radiologically
evident.Results. The true objective response rate was 0%. However, disease
stabilization and clinical benefit response were observed in five patients (70%)
for 13-96 weeks.Discussion. Postponing the inevitable death with a relatively
non-toxic treatment, is, in our opinion, an important issue especially in young
patients.Thus it may be justified and warranted to investigate the activity of
gemcitabine in a larger group of patients with bone sarcomas.
PMCID: PMC2408365
PMID: 18521428 [PubMed]
19. Sarcoma. 1999;3(2):85-8. doi: 10.1080/13577149977695.
Kollender Y(1), Shabat S, Nirkin A, Issakov J, Flusser G, Merimsky O, Meller I.
Author information:
(1)The National Unit of Orthopedic Oncology The Tel-Aviv Sourasky Medical Center
Tel Aviv Israel.
Background. The origin of Ewing's sarcoma in a periosteal location is rare and
not clearly documented. Other malignant bone tumors appear to have a somewhat
better prognosis when confined between periosteum and bone. Is it the same for
periosteal Ewing's sarcoma?Methods. We describe two new cases and comprehensively
review the literature consisting of 18 documented cases since the condition was
first described in 1986 (S.M. Bator.Cancer 58:1781- 4).Results. Periosteal
Ewing's sarcoma differs from the other forms of Ewing's sarcoma in terms of sex
predominance, location of tumor, surgical stage at presentation and typical
imaging studies. Eighteen out of the 20 patients were reported to be alive with
no evidence of disease.Conclusions. It seems that the prognosis of this rare
variant of Ewing's sarcoma family of tumors might be better but the small number
of cases precludes such a firm conclusion.
PMCID: PMC2395413
PMID: 18521268 [PubMed]
20. Sarcoma. 1998;2(3-4):205-7. doi: 10.1080/13577149877993.
Primary liposarcoma of the mediastinum.
Greif J(1), Marmor S, Merimsky O, Kovner F, Inbar M.
Author information:
(1)Pulmonary Division Tel-Aviv Sourasky Medical Center and the Sackler Faculty of
Medicine Tel-Aviv University Tel-Aviv Israel.
Patient. A 62-year-old man presented with effort dyspnea, non-productive cough
and weakness of 4 month duration. He had no findings on physical
examination.Discussion. Chest X-ray revealed a large mass in the left anterior
mediastinum. Computerized tomography of the chest showed a well-delineated
homogeneous mediastinal mass with fat-equivalent density and a small pleural
effusion. Fiberoptic bronchoscopy revealed narrowing of the left main bronchus,
secondary to external compression. The bronchial mucosa was normal and brush
cytology was negative. A CT-guided fine needle aspiration (FNA) of the mass
yielded fragments of cells embedded in myxoid background material and closely
packed atypical lipoblasts, compatible with liposarcoma. The patient underwent a
left lateral thoracotomy and margibnal resection of the mass. The
histopathological examination confirmed the diagnosis of mixed-type liposarcoma,
consisted of myxoid and pleomorphic liposarcoma. Postoperative two-field
radiation therapy was delivered to the mediastinum for a total midplane dose of
40 Gy. After a disease-free interval of 8 months the disease recurred in the
mediastinum and pleura. Palliative chemotherapy achieved a short duration partial
response but the patient succumbed to local recurrence 2 years after the
diagnosis.
PMCID: PMC2395397
PMID: 18521256 [PubMed]
21. Sarcoma. 2008;2008:825093. doi: 10.1155/2008/825093.
Targeting mTOR in HIV-Negative Classic Kaposi's Sarcoma.
Merimsky O(1), Jiveliouk I, Sagi-Eisenberg R.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky
Medical Center, 6 Weitzman Street, Tel-Aviv 64239, Israel.
A 66-year old female with HIV-negative classic Kaposi's sarcoma responded to mTOR
targeting by rapamycin. The response was well documented by PET-CT. This case
provides supporting evidence that the mTOR pathway may be important in the
tumorigenesis of KS and that rapamycin may have activity in this disease.
PMCID: PMC2391286
PMID: 18509482 [PubMed]
22. Eur J Surg Oncol. 2009 Feb;35(2):209-14. doi: 10.1016/j.ejso.2008.01.007. Epub
2008 Mar 4.
Efficacy of high vs low dose TNF-isolated limb perfusion for locally advanced
soft tissue sarcoma.
Nachmany I(1), Subhi A, Meller I, Gutman M, Lahat G, Merimsky O, Klausner JM.
Author information:
(1)Department of Surgery B, Tel Aviv Sourasky Medical Center, Sackler School of
Medicine, Tel Aviv University, Tel Aviv, Israel. ido.nachmany@gmail.com
AIMS: The administration of a high dose of rTNF-alpha (3-4 mg) and Melphalan via
isolated limb perfusion (ILP) for patients with locally advanced limb STS was
shown to be effective. Reports that a low dose of TNF (1mg) is as effective, led
to the adoption of the low dose regimen as the treatment of choice. The purpose
of this study was to compare two groups of patients with locally advanced limb
STS, that was treated with high and low dose TNF-ILP, in terms of limb
preservation.
METHODS: Retrospective study of 41 patients who underwent ILP, with "high dose"
(HD) and "low dose" (LD) TNF. ILP/TNF was performed on candidates to either
amputation or significantly mutilating surgery without this treatment. In both
groups, all patients, with the exception of three in each group, underwent
resection of the residual tumor or tumor bed or limb 8-12 weeks after the
procedure.
RESULTS: In the HD group, marked tumor softening occurred within 48 h, and in
tumors protruding through the skin, hemorrhagic necrosis was evident within 24h.
The overall response rate was 65.2%. Five patients achieved a CR and 10 had a PR;
in five of these patients >90% necrosis of the tumor occurred. In eight patients,
only minimal regression was observed (stabilization of disease). The rate of limb
sparing was 69.5%. In the LD group, the overall response rate was 30.7%. CR was
achieved in one patient. PR was observed in two. Two patients were lost to follow
up. Of the remaining 15 patients, limb preservation was achieved in 53.3%.
CONCLUSION: Despite the retrospective comparison and possible selection bias, it
is possible to raise the concern that at least some patients may benefit from a
higher TNF dose perfusion in ILP for advanced limb STS.
PMID: 18295442 [PubMed - indexed for MEDLINE]
23. Isr Med Assoc J. 2007 Nov;9(11):810-2.
A histopathological review of gastrointestinal related mesenchymal tumors: the
hidden GIST.
Issakov J(1), Jiveliouk I, Nachmany I, Klausner J, Merimsky O.
Author information:
(1)Unit of Bone and Soft Tissue Pathology, Tel Aviv Sourasky Medical Center, Tel
Aviv, Israel.
BACKGROUND: The diagnosis of gastrointestinal stromal tumors is based on
documentation of c-KIT and platelet-derived growth factor-alpha receptors or
specific c-KIT mutations. Before the diagnosis of GIST was possible, all cases
had been classified as sarcomas or benign tumors.
OBJECTIVES: To identify cases of GIST formerly diagnosed as abdominal or
retroperitoneal mesenchymal tumors.
METHODS: We reviewed the archive material on all surgical cases diagnosed as
gastrointestinal related malignant mesenchymal tumors or GIST in our medical
center during the last decade (1995-2004).
RESULTS: Sixty-eight cases of retroperitoneal soft tissue sarcoma were
identified. Thirty-eight were reconfirmed to be GIST, 19 were newly diagnosed as
GIST (the hidden cases), 8 cases were re-diagnosed as mesenchymal tumors, and 3
cases of sarcoma remained sarcomas. Of all the GIST tumors, c-KIT-positive and
PDGFRalpha-positive tumors were more characteristic of primary gastric tumors,
while c-KIT-positive and PDGFRalpha-negative tumors were found in the colorectal
area. The c-KIT-negative and PDGFRalpha-positive cases were of gastric origin.
CONCLUSIONS: Any c-KIT-negative malignant mesenchymal mass located near the
proximal gastrointestinal tract should also be stained for PDGFRalpha to
differentiate between GIST and other soft tissue sarcomas. Practically, formerly
diagnosed abdominal or retroperitoneal soft tissue sarcomas should be reviewed to
identify patients with misdiagnosed GIST and thereby avoid future unnecessary and
ineffective chemotherapy.
PMID: 18085040 [PubMed - indexed for MEDLINE]
24. Oncol Rep. 2007 Dec;18(6):1577-81.
Synovial sarcoma of the extremities and trunk: a long-lasting disease.
Gofman A(1), Issakov J, Kollender Y, Soyfer V, Dadia S, Jiveliouk I, Flusser G,
Bickels J, Meller I, Merimsky O.
Author information:
(1)National Unit of Orthopedic Oncology, Tel-Aviv Sourasky Medical Center,
affiliated with Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 64239,
Israel.
Synovial sarcoma (SS) of an extremity or trunk is relatively rare and is
approached by limb sparing surgery (LSS), radiation therapy (RT) and
chemotherapy. We conducted a retrospective analysis of the clinical and
histopathological data of 73 patients with proven SS. At a median follow-up time
of 6 years, local recurrence was seen in 17.8 and systemic recurrence 35.6% of
patients (local-only, 6.8; systemic-only, 24.6; combined, 11%). The 10-year local
recurrence-free survival (LRFS), systemic recurrence-free survival (SRFS) and
overall survival (OS) rates were 78, 68 and 61%, respectively. LRFS was
significantly better in patients treated with isolated limb perfusion (ILP); SRFS
was influenced by the delay until diagnosis. The practical aspects of our
observations are the need for long-term follow-up in order to diagnose
recurrences, the fact that not all local or distant recurrences are necessarily
associated with a shortening of OS time and the important role of induction ILP
with TNF in cases of extremity SS.
PMID: 17982647 [PubMed - indexed for MEDLINE]
25. Gynecol Obstet Invest. 2008;65(2):89-95. Epub 2007 Sep 18.
The complexity of management of pregnancy-associated malignant soft tissue and
bone tumors.
Molho RB(1), Kollender Y, Issakov J, Bickels J, Flusser G, Azem F, Alon A, Inbar
MJ, Meller I, Merimsky O.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky
Medical Center, Tel-Aviv, Israel.
OBJECTIVE: The incidence of musculoskeletal tumors during pregnancy is very low.
The aim of this study was to summarize our experience in treating a large cohort
of pregnant patients diagnosed with these rare tumors.
METHODS: Women diagnosed with musculoskeletal tumors during pregnancy or
immediately after delivery were identified retrospectively in our database
between 1996 and 2006. Relevant maternal and neonatal data were collected.
RESULTS: Twenty patients, 8 with bone sarcomas (BS) and 12 with soft tissue
sarcomas (STS) were identified. Two women were treated by wide excision of mass
during pregnancy. In all other cases oncological treatment was delayed until
delivery or termination of pregnancy. Vaginal delivery was possible in 9
patients, cesarean section was performed in 7, spontaneous abortion occurred in
1, and 3 underwent termination of pregnancy. Three newborns were premature, but
normal growth and development were observed. Different techniques of fertility
preservation were used in our patients. Five patients with BS and 5 patients with
STS received preoperative chemotherapy, with different grades of toxicity. The
degree of tumor necrosis tended to correlate with dose-intensity of chemotherapy.
Seven patients with BS received adjuvant chemotherapy. Two patients with STS
received adjuvant chemotherapy, two - radiotherapy, and four - both modalities.
Median disease-free survival was 15.1 months, median overall survival - 25.4
months.
CONCLUSIONS: Musculoskeletal tumors diagnosed during pregnancy, or after
delivery, do not appear to have a significant impact on the prognosis. A
multidisciplinary team should tailor the oncological approach individually.
(c) 2008 S. Karger AG, Basel.
PMID: 17878735 [PubMed - indexed for MEDLINE]
26. Int J Oncol. 2007 Jul;31(1):225-32.
Molecular impacts of rapamycin-based drug combinations: combining rapamycin with
gemcitabine or imatinib mesylate (Gleevec) in a human leiomyosarcoma model.
Merimsky O(1), Gorzalczany Y, Sagi-Eisenberg R.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, The Tel-Aviv
Sourasky Medical Center, Tel Aviv, Israel.
Drug combinations may provide a therapeutic benefit in treating cancer patients.
However when considering a drug combination, it is important to assess how the
molecular impact of the combination relates to the effects manifested by each
drug alone and whether or not it varies depending on the tumor type. In this
study, we have analyzed the molecular impact on a human leiomyosarcoma cell line
(SK-LMS-1) of a combination consisting of the mTOR inhibitor rapamycin and either
the anti-metabolite drug gemcitabine (Gemzar) or the protein tyrosine kinase
inhibitor imatinib mesylate (Gleevec, STI571). We show that imatinib mesylate
depolarizes the mitochondrial membrane potential (DeltaPhim) and inhibits protein
tyrosine phosphorylation, but displays only minor effects on cell proliferation
when added alone or in combin-ation with rapamycin. Gemcitabine or rapamycin,
when added alone, inhibit protein tyrosine phosphorylation as well as
phosphorylation of the MAP kinases ERK1/2. Both drugs also affect the cell cycle,
arresting the cells at the S or G1 phase respectively. Rapamycin elevates
significantly DeltaPhim but produces only a moderate effect on cell growth.
Gemcitabine inhibits considerably cell growth but exerts no effect on DeltaPhim.
Combining gemcitabine and rapamycin produces a major effect on the cell cycle,
elevates the DeltaPhim even further and maintains the molecular impacts exerted
by each single drug. Therefore, consistent with our clinical observation, these
results suggest that combining gemcitabine and rapamycin may be beneficial in
treating leiomyosarcoma patients.
PMID: 17549426 [PubMed - indexed for MEDLINE]
27. J Bone Joint Surg Br. 2006 Dec;88(12):1647-51.
Liposarcoma in adult limbs treated by limb-sparing surgery and adjuvant
radiotherapy.
Issakov J(1), Soyfer V, Kollender Y, Bickels J, Meller I, Merimsky O.
Author information:
(1)Department of Pathology, Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel.
Between December 1995 and March 2003, 38 adult patients with intermediate or
high-grade liposarcoma in a limb were treated by limb-sparing surgery and
post-operative radiotherapy. The ten-year local recurrence-free survival was 83%,
the ten-year metastasis-free survival 61%, the ten-year disease-free survival 51%
and the ten-year overall survival 67%. Analysis of failure and success showed no
association with the age of the patients, gender, the location of the primary
tumour, the type of liposarcoma and the quality of resection. Our results
indicate that liposarcoma may recur even ten years after the end of definitive
therapy and may spread to unexpected sites as for soft-tissue sarcoma.
PMID: 17159180 [PubMed - indexed for MEDLINE]
28. Radiother Oncol. 2005 Dec;77(3):295-300. Epub 2005 Nov 21.
Limb sparing approach: adjuvant radiation therapy in adults with intermediate or
high-grade limb soft tissue sarcoma.
Merimsky O(1), Soyfer V, Kovner F, Bickels J, Issakov J, Flusser G, Meller I,
Ofer O, Kollender Y.
Author information:
(1)Sackler School of Medicine, Tel-Aviv University, Israel.
BACKGROUND: Limb soft tissue sarcomas (STS) are currently treated with limb
sparing surgery (LSS) followed by radiation therapy (RT).
PATIENTS AND METHODS: Between October 1994 and October 2002, 133 adult patients
with intermediate or high-grade limb STS were approached by LSS+RT.
RESULTS: RT related toxicity was manageable, with a low rate of severe effects.
At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated
local failure, and 35 of systemic spread w/o local failure. DFS and OS were
influenced by disease stage II vs I, primary site in the upper limb vs lower
limb, MPNST vs other types, induction therapy vs no induction, adequate resection
vs marginal resection or involved margins, and good response to induction therapy
vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or
late toxicity of RT, or the interval of time between the date of definitive
surgery and the start of RT did not affect DFS and or OS.
CONCLUSIONS: The RT protocol is applicable in the era of complicated, expensive
and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS
are satisfactory.
PMID: 16300847 [PubMed - indexed for MEDLINE]
29. Oncol Rep. 2005 Oct;14(4):1071-6.
A single-team experience of limb sparing approach in adults with high-grade
malignant fibrous histiocytoma.
Issakov J(1), Kollender Y, Soyfer V, Bickels J, Flusser G, Meller I, Merimsky O.
Author information:
(1)Unit of Musculoskeletal Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv,
Israel.
Malignant fibrous histiocytoma (MFH) is the most common subtype of soft-tissue
sarcoma (STS). When located in a limb, MFH, is currently treated with limb
sparing surgery (LSS) followed by radiation therapy (RT). During 8 years, 42
adult patients with high-grade limb MFH were approached by LSS and RT. Our
results reflect a single-team experience and point to several important
conclusions. High grade MFH, treated by conservative approach, lead to a 10-year
relapse-free survival of 62% and a 10-year overall survival rate of 80%.
Recurrences of MFH tend to occur during the first 2 years. Relapse-free survival
was affected mainly by location in the lower limb vs. the upper limb,
irrespective of the tumor size. Patients who had their diagnostic biopsies in
another medical center had a greater tendency to local and systemic relapse. It
seems that the most important clues for disease-free survival are the team
experience and cooperation. All other factors are tumor-biology dependent, and
thus far are beyond our control.
PMID: 16142374 [PubMed - indexed for MEDLINE]
30. Int J Mol Med. 2004 Nov;14(5):931-5.
Targeting metastatic leiomyosarcoma by rapamycin plus gemcitabine: an intriguing
clinical observation.
Merimsky O(1).
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, The Tel-Aviv
Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel.
The emerging anti-cancer approach is based on combining a 'traditional' cytotoxic
drug with a 'signaling' blocking agent. Such combination, if designed and applied
properly, may increase selectivity towards tumor cells. The use of such
combinations requires smart planning and choice of the drugs to be combined,
their proper dosing as well as correct sequence and schedule of application. The
combination of the anti-metabolite gemcitabine and the mTOR blocker, rapamycin,
has achieved an impressive response in a patient with metastatic leiomyosarcoma.
PMID: 15492868 [PubMed - indexed for MEDLINE]
31. Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1468-73.
Radiotherapy for spinal cord compression in patients with soft-tissue sarcoma.
Merimsky O(1), Kollender Y, Bokstein F, Issakov J, Flusser G, Inbar MJ, Meller I,
Bickels J.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Tel-Aviv Sourasky Medical Center and
Tel-Aviv University Sackler School of Medicine, Tel-Aviv, Israel.
PURPOSE: Spinal metastases of soft-tissue sarcoma (STS) occur rarely and pose a
therapeutic problem. Although wide resection is warranted for best local control,
it is rarely feasible. A radiotherapy (RT) dose of 70 Gy is usually needed to
treat limb STS, but only 45 Gy can be given to the spine. In the present series,
we report our experience using RT to treat spinal cord compression (SpCC)
associated with STS.
METHODS AND MATERIALS: The medical files of 19 adult patients with STS and SpCC
were reviewed. RT was considered in all the cases, together with steroids and
analgesics. The prescribed dose was 30 Gy in 10 fractions within 12 days. The
effect of treatment was evaluated on a clinical basis.
RESULTS: Twenty-three events of SpCC were found. The prevailing symptom was pain.
The Karnofsky performance status was 40-70% at presentation. RT was given in all
but 1 patient and surgical decompression in 3. Small, but important, improvements
in signs and Karnofsky performance status were noted in 14 of 23 cases of SpCC,
expressed mainly by pain alleviation and restoration of independence. The median
survival after the diagnosis of SpCC was 5 months.
CONCLUSION: Radiotherapy is an important tool in palliating SpCC in patients with
STS.
PMID: 15050325 [PubMed - indexed for MEDLINE]
32. Isr Med Assoc J. 2004 Jan;6(1):34-8.
Palliative treatment for advanced or metastatic osteosarcoma.
Merimsky O(1), Kollender Y, Inbar M, Meller I, Bickels J.
Author information:
(1)Unit of Soft Tissue and Bone Oncology, Tel Aviv Sourasky Medical Center, Tel
Aviv, Israel. oferm@tasmc.health.gov.il
PMID: 14740508 [PubMed - indexed for MEDLINE]
33. Isr Med Assoc J. 2003 Apr;5(4):264-7.
Gestation-related malignant musculoskeletal tumors.
Merimsky O(1), Inbar M, Issakov J, Kollender Y, Flusser G, Meller I, Bickels J.
Author information:
(1)Unit of Bone and Soft Tissue Oncology, Tel Aviv Sourasky Medical Center, Tel
Aviv, Israel. merimsky@zahav.net.it
BACKGROUND: The incidence of malignant musculoskeletal tumors during pregnancy is
very low. The paucity of data precludes the drawing of solid conclusions
regarding a standard approach.
OBJECTIVES: To summarize our experience treating 13 pregnant women with malignant
soft tissue or bone tumors.
METHODS: We conducted a retrospective analysis of 13 cases of patients with
either soft tissue or bone sarcoma that developed or progressed during pregnancy
or immediately after delivery.
RESULTS: The clinical presentation of the tumors was a growing mass and/or
increasing pain and disability. Most of the masses were located in the lower part
of the body and were of considerable size. Treatment given during gestation was
limited to wide excision of the mass in the 28th week of gestation in one
patient. All the patients reported disease progression during gestation. Vaginal
delivery was possible in eight patients with no complications, cesarean section
was carried out in three women, spontaneous miscarriage occurred in one and
termination of pregnancy was performed in one patient.
CONCLUSIONS: The diagnostic and therapeutic approaches should be tailored
specifically in every pregnant woman in whom sarcoma is suspected.
PMID: 14509131 [PubMed - indexed for MEDLINE]
34. Oncol Rep. 2003 Sep-Oct;10(5):1593-9.
Induction chemotherapy for bone sarcoma in adults: correlation of results with
erbB-4 expression.
Merimsky O(1), Kollender Y, Issakov J, Inbar M, Flusser G, Benayahu D, Meller I,
Bickels J.
Author information:
(1)Unit of Soft Tissue and Bone Oncology, Division of Oncology, The Tel-Aviv
Sourasky Medical Center, Tel-Aviv 64239, Israel. merimsky@zahav.net.il
Tumor response to preoperative chemotherapy is an important prognostic factor for
localized, operable extremity osteosarcoma. Other clinical variables include
tumor size and location, age and sex, and serum enzymes. Advances in molecular
oncology yielded a second group of factors such as multidrug resistance status,
loss of heterozygosity of RB gene, and HER2/erbB-2 expression. The aim of this
study was to investigate the expression and the prognostic value of the newly
described erbB-4 receptor in specimens from adults with bone sarcomas treated by
pre- and postoperative chemotherapy. Thirty-three patients with non-metastatic
bone sarcoma have been treated by two doxorubicin-based induction chemotherapy
regimen, followed by limb sparing surgery and tailored adjuvant chemotherapy.
Pre-chemotherapy tissue specimens were investigated for the expression of erbB-4
receptor and post-induction specimens were assessed for pathological response.
The clinical response rates were 32-36%. The degree of induced necrosis was
correlated with the disease-free survival (DFS). Patients achieving >/=90%
necrosis had an improved DFS over patients with poor histological response.
ErbB-4 expression was significantly associated with poor histologic response and
shorter DFS. ErbB-4 expression may be used for prognostication of adults with
bone sarcomas.
PMID: 12883746 [PubMed - indexed for MEDLINE]
35. Cancer. 2003 Jun 1;97(11):2830-8.
Role of adjuvant cryosurgery in intralesional treatment of sacral tumors.
Kollender Y(1), Meller I, Bickels J, Flusser G, Issakov J, Merimsky O, Marouani
N, Nirkin A, Weinbroum AA.
Author information:
(1)National Orthopedic Oncology Unit, Tel-Aviv Sourasky Medical Center, Sackler
Faculty of Medicine, Tel Aviv University, Israel.
BACKGROUND: Cryosurgery is an adjuvant surgical technique for the treatment of
benign aggressive, low-grade malignant and metastatic tumors of long bones. It
has been used rarely to treat sacral tumors, mainly because of potential damage
to nerves, blood vessels, and intrapelvic organs. The authors described their
experience with this procedure and provided medium and long-term follow-up
results.
METHODS: Fifteen procedures of cryosurgery of the sacrum were performed in 14
patients to improve the therapeutic outcome of a variety of tumors. The patient
group included 7 males and 7 females with a mean age of 42 +/- 24 years. Three
patients were younger than 20 years of age. The procedures were performed at the
Tel Aviv Sourasky Medical Center between January 1991 and January 1999. There
were seven benign aggressive lesions (four giant cell tumors and three aneurysmal
bone cysts), one benign schwannoma, one low-grade chondrosarcoma, five metastatic
carcinomas, and one high-grade Ewing sarcoma, all localized at level S(2) or
higher. Eight of the bone tumors also involved significant anterior or posterior
soft tissue. All patients had severe preoperative pain radiating to the buttocks,
perineum, and lower limbs and 9 (64%) patients had bladder and/or rectal
dysfunction. Invasive diagnostic procedures and radiation (if warranted) preceded
surgery. Sacral posterior fenestration and burr drilling were followed by
two-cycle cryosurgery using the open pour technique or the argon-helium-based
heat-freeze system.
RESULTS: All interventions were performed under combined general and regional
anesthesia and concluded uneventfully with moderate blood loss. Thirteen patients
were discharged home after 8 +/- 5 days (one patient remained hospitalized for 30
days). Only two patients experienced local disease recurrence during a 3-11-year
follow-up period: one was retreated successfully by cryosurgery and the other
underwent sacrectomy and radiotherapy elsewhere, with a subsequent loss of
visceral functions. No patient suffered chronic pain, deep wound infections, or
significant neurologic deficits and all were satisfied with the esthetic outcome.
CONCLUSIONS: Cryosurgery is a conservative, feasible, and safe adjuvant technique
in the treatment of sacral tumors. It is associated with minimal permanent
neurologic and vascular injury compared with sacrectomy.
Copyright 2003 American Cancer Society.
PMID: 12767097 [PubMed - indexed for MEDLINE]