מאמרים בתחום הטיפול הקרינתי
1. 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.
(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
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]
2. Lung. 2014 Oct;192(5):759-63. doi: 10.1007/s00408-014-9604-7. Epub 2014 Jun 26.
EGFR mutation testing practice in advanced non-small cell lung cancer.
Bar J(1), Cyjon A, Flex D, Sorotsky H, Biran H, Dudnik J, Peylan-Ramu N, Peled N,
Nechushtan H, Gips M, Katsnelson R, Rosenberg SK, Merimsky O, Onn A, Gottfried M.
(1)Department of Oncology, Institute of Oncology, Sheba Medical Center, Tel
Hashomer, 52621, Ramat Gan, Israel, email@example.com.
PURPOSE: Testing tumor samples for the presence of a mutation in the epithelial
growth factor receptor (EGFR) gene is recommended for advanced non-squamous
non-small cell lung cancer (NSCLC) patients. We aimed to collect data about
common practice among Medical Oncologists treating lung cancer patients,
regarding EGFR mutation testing in advanced NSCLC patients.
METHODS: An internet-based survey was conducted among members of the Israeli
Society for Clinical Oncology and Radiotherapy involved in the treatment of lung
RESULTS: 24 Oncologists participated in the survey. The participants encompass
the Oncologists treating most of the lung cancer patients in Israel. 79% of them
use EGFR testing routinely for all advanced NSCLC patients. Opinions were split
regarding the preferable biopsy site for EGFR testing material. 60% of
participants recommend waiting for EGFR test results prior to initiation of
CONCLUSIONS: EGFR testing is requested in Israel routinely by most treating
Oncologists for all advanced NSCLC patients, regardless of histology. In most
cases, systemic treatment is deferred until the results of this test are
PMID: 24964874 [PubMed - indexed for MEDLINE]
3. 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.
(1)The Department of General Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv,
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]
4. Lancet Oncol. 2014 Jan;15(1):59-68. doi: 10.1016/S1470-2045(13)70510-2. Epub 2013
Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III
non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.
Butts C(1), Socinski MA(2), Mitchell PL(3), Thatcher N(4), Havel L(5), Krzakowski
M(6), Nawrocki S(7), Ciuleanu TE(8), Bosquée L(9), Trigo JM(10), Spira A(11),
Tremblay L(12), Nyman J(13), Ramlau R(14), Wickart-Johansson G(15), Ellis P(16),
Gladkov O(17), Pereira JR(18), Eberhardt WE(19), Helwig C(20), Schröder A(20),
Shepherd FA(21); START trial team.
Collaborators: Shepherd F, Butts C, Thatcher N, Socinski M, Mitchell P, Talbot D,
Gillen D, Whang-Peng J, Thirwell M, Seeber S, Braun D, Schröder A, Falk M,
Günther B, Marschner JP, Helwig C, Loos A, Tyroller K, Schüler A, Ferrande L,
Gaumond B, Olchowka K, Koh P, Mackiewicz M, Sylvester E, Wallis N, Joerg I,
Schick R, Munn J, Best M, Campbell A, Laszczewska V, Parvez T, Ferro A, Tremblay
L, Sadjadian P, Smit E, Park K, Kotz K, Borghaei H, Stehle I, Ismael C, Alam Z,
Engel-Riedel W, Stigt J, García Girón C, Kumar K, Oton A, Jäger E, Pasccon GV,
von Ksienski D, Pawel J, van den Borne B, Trigo JM, Lester E, Nader D, Kortsik C,
Martin C, Murray N, Serke M, van den Heuvel M, Vazquez S, March R, Li Z, Wolf M,
Pallotta M, MacNeil M, Georgoulias V, van Ojik H, López Vivanco G, Masri M,
Espinoza A, Rüttinger D, Perazzo F, Hirsh V, Kosmidis P, Krouwels F, Paredes A,
Shinn L Jr, Limentani S, Eschbach C, Ponce W, Findlay B, Pectasides D,
Chmielowska E, Viñolas N, Mirtsching B, Pincus S, Gahn B, Fein L, Burkes R,
Syrigos K, Jagiello-Gruszfeld A, Massuti B, Okazaki I, Young D, Kollmeier J,
Zarbá J, MacCormick R, Fountzilas G, Kozielski J, Gonzalez-Larriba JL, Saleh M,
Nugent F 3rd, Gütz S, Bella S, Wang J, Samantas E, Krzakowski M, Barragán PL,
Curran C, Chaudhry A, Wilke H, Bagnes C, Sun Y, Lee V, Lesniewski-Kmak K, Alonso
G, Gabrail N, Ndum P, Reck M, Mitchell P, Koubková L, Mok T, Ramlau R, Bosch J,
Abbott K, Beall C, Shepherd F, Millward M, Reiterer P, Albert I, Rysz-Postawa B,
Moreno MA, Bellam S, Nieva J, Maksymiuk A, Boyer M, Roubec J, Losonczy G, Labij
V, de Castro J, Charu V, Modi S, Butts C, McCaffrey E, Salajka F, Szima B,
Rusinowska Z, Wichardt-Johansson G, Erlich R, Dudek A, Ellis P, Pavlakis N, Havel
L, Zsiray M, Szczesna A, Ewers SV, Page R, Ghazal H, Lee C, Crombie C, Zemanová
M, Szabó P, Freier B, Henriksson R, Rao H, Gitlitz B, Desjardins P, Kirsten F,
Hansen O, Bittner N, Kus J, Nyman J, Sanborn R, Harrer G, Vergidis D, Pirker R,
Ryberg M, Bittner N, Sawrycki P, Nilsson K, Bruno D, Mehdi A, Cohen V, Kolb R,
Louridi JB, Chacko R, Chojnacka M, Bergström S, Shah S, Jones C, Bebb G,
Mohn-Staudner A, Robinet G, Raja R, Nawrocki S, Zippelius A, Shirinian M,
Gotovkin E, Soulières D, Greil R, Zalcman G, Julka PK, Fijuth J, Pless M, Abdel
Karim I, Soo R, Thropay J, Hilbe W, Choma D, Digumarti R, Barata FJ, Mach N,
Neerukonda L, Kasan P, Akunyili I, Kropfmüller R, Verkindre C, Advani S, Teixeira
E, Yang CH, Bonomi P, Packan T, Argiris A, Samonigg H, Dumont P, Vamsy M,
Almodovar MT, Liu MC, Rakkar A, Berzinec P, Edelman M, Vansteenkiste J, Tourani
JM, O'Byrne K, Araújo A, Hsia TC, Rao R, Kang JH, Natale R, Lambrechts M, Gervais
R, Cyjon A, Dediu M, Chang GC, Dowlati A, Kim SW, Ottensmeier C, Humblet Y,
Schott R, Dudnik J, Anghel R, Chen YM, Weiss J, Lee JS, Collinson M, Duplaquet F,
Spaeth D, Gottfried M, Ciuleanu TD, Tsao CH, Spira A, Kim JH, Thomas G, Louis R,
Barlesi F, Merimsky O, Volovat C, Kuo HP, Langer C, Heo DS, O'Brien M, Clinckart
F, Fabre-Guillevin E, Peylan-Ramu N, Ganea Motan DE, Huang MS, Vrindavanam N,
Gebbia V, MacGregor C, Verhoeven D, Pibarot M, Sulkes A, Patran M, Su WC, Bhanja
U, Ciardiello F, Tjulandin S, de Azevedo S, Westeel V, Wollner M, Sirbu D, Lin
MC, Hoffman S, Grossi F, Popov V, Barrios CH, Mornex F, Onn A, Cheporov S, Price
A, Bednar M, Aglietta M, Goldberg V, Delgado G, Thomas M, Platania M, Gladkov O,
Snee M, Bhaskar B, Contu A, Medvedev V, Franke FA, Waller C, Siena C, Mikhaylov
S, Dorey N, Caputto S, Gridelli C, Khasanov R, Malzyner A, Eberhardt W, Amadori
D, Lubennikov V, Marshall E, Chen LC, Guevara Torres A, Santoro A, Nugué P,
Schneller F, De Marinis F, Akhmadullina L, Ezhil M, West H, Trigueros Velázquez
M, Scagliotti G, Pizão, Griesinger F, Longo L, Byakhov M, Hicks J, Berg A,
Ramírez Márquez M, Tiseo M, Segalla, Hildebrandt G, Martoni A, Moiseyenko V,
Taylor P, Hays J, Arrieta Rodriguez OG, Caffo O, Mathias CM, Huber R, Witt C,
Murad A, Höffken G, Gorini C, Zukin M, Iacobelli S, Pereira J, Schreiber J,
Lancet Oncol. 2014 Jan;15(1):5-6.
BACKGROUND: Effective maintenance therapies after chemoradiotherapy for lung
cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific
cancer immunotherapy tecemotide improves survival in patients with stage III
unresectable non-small-cell lung cancer when given as maintenance therapy after
METHODS: The phase 3 START trial was an international, randomised, double-blind
trial that recruited patients with unresectable stage III non-small-cell lung
cancer who had completed chemoradiotherapy within the 4-12 week window before
randomisation and received confirmation of stable disease or objective response.
Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy
(stable disease vs objective response), delivery of chemoradiotherapy (concurrent
vs sequential), and region using block randomisation, and were randomly assigned
(2:1, double-blind) by a central interactive voice randomisation system to either
tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo
were given every week for 8 weeks, and then every 6 weeks until disease
progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or
saline (before placebo) was given once before the first study drug
administration. The primary endpoint was overall survival in a modified
intention-to-treat population. This study is registered with ClinicalTrials.gov,
FINDINGS: From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly
assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from
the primary analysis population as a result of a clinical hold, resulting in
analysis of 829 patients in the tecemotide group and 410 in the placebo group in
the modified intention-to-treat population. Median overall survival was 25.6
months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with
placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received
previous concurrent chemoradiotherapy, median overall survival for the 538 (65%)
of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8)
compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned
to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received
previous sequential chemoradiotherapy, overall survival did not differ between
the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the
placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0],
respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen
with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024
patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo
group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia
(23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency
with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the
placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous
system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ
INTERPRETATION: We found no significant difference in overall survival with the
administration of tecemotide after chemoradiotherapy compared with placebo for
all patients with unresectable stage III non-small-cell lung cancer. However,
tecemotide might have a role for patients who initially receive concurrent
chemoradiotherapy, and further study in this population is warranted.
FUNDING: Merck KGaA (Darmstadt, Germany).
Copyright © 2014 Elsevier Ltd. All rights reserved.
PMID: 24331154 [PubMed - indexed for MEDLINE]
5. Br J Radiol. 2013 Aug;86(1028):20130258. doi: 10.1259/bjr.20130258. Epub 2013 May
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.
(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.
PMID: 23709514 [PubMed - indexed for MEDLINE]
6. 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.
(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
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
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
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]
7. Oncol Rep. 2012 Aug;28(2):721-7. doi: 10.3892/or.2012.1824. Epub 2012 May 18.
Efficacy and safety of first-line erlotinib in elderly patients with advanced
non-small cell lung cancer.
Merimsky O(1), Cheng CK, Au JS, von Pawel J, Reck M.
(1)Division of Oncology, Tel Aviv Medical Center, Tel-Aviv 64239, Israel.
TaRceva LUng cancer Survival Treatment (TRUST) was an open-label, phase IV study
of advanced non-small cell lung cancer (NSCLC). Patients failing or unsuitable
for chemotherapy or radiotherapy received erlotinib 150 mg/day until progression.
We examined a subpopulation of elderly patients (≥70 years) receiving first-line
erlotinib (n=485) in TRUST. In this subpopulation, disease control rate (n=356
with best response data available) was 79% (vs. 69% for the overall TRUST
population; p<0.0001); median progression-free survival (PFS) was 4.57 months
[95% confidence interval (CI), 3.68-5.22]; median overall survival (OS) was 7.29
months (95% CI, 6.27-8.67); and one-year survival, was 36.6%. PFS and OS were
significantly longer in patients developing rash, compared to those without, and
in those with good performance status (PS; 0/1), compared to poor PS (≥2).
Eighty-seven subpopulation patients (18%) had an erlotinib-related AE; other than
the protocol-defined frequent adverse events (AEs); 4% had a grade ≥3
erlotinib-related AE, 7% had an erlotinib-related serious AE. In the
subpopulation, dose reductions were required in 27%, most (97%) were reductions
to 100 mg/day; treatment was discontinued in 10%, and one death was associated
with treatment-related toxicity (<1%). Erlotinib was effective and well-tolerated
and may be considered for elderly patients with advanced NSCLC who are unsuitable
for standard first-line chemotherapy or radiotherapy.
PMID: 22614912 [PubMed - indexed for MEDLINE]
8. Oncologist. 2010;15(3):317-26. doi: 10.1634/theoncologist.2009-0257. Epub 2010
Do oncologists engage in bereavement practices? A survey of the Israeli Society
of Clinical Oncology and Radiation Therapy (ISCORT).
Corn BW(1), Shabtai E, Merimsky O, Inbar M, Rosenbaum E, Meirovitz A, Wexler ID.
PURPOSE: We sought to determine the level of involvement of oncologists in
bereavement rituals after a patient dies.
SUBJECTS AND METHODS: Members of the Israeli Society for Clinical Oncology and
Radiation Therapy (ISCORT) were surveyed. The survey instrument consisted of
questions regarding participation in bereavement rituals for patients in general
and those with whom the oncologist had a special bond. Oncologists were queried
as to the reasons for nonparticipation in bereavement rituals.
RESULTS: Nearly 70% of the ISCORT membership (126 of 182) completed the survey
tool. Respondents included radiation, surgical, and medical oncologists. In
general, oncologists rarely participated in bereavement rituals that involved
direct contact with families such as funerals and visitations. Twenty-eight
percent of physicians at least occasionally participated in rituals involving
direct contact whereas 45% had indirect contact (e.g., letter of condolence) with
the family on an occasional basis. There was significantly greater involvement in
bereavement rituals when oncologists developed a special bond with the patient.
In a stepwise linear regression model, the only factor significantly associated
with greater participation in bereavement rituals was self-perceived spirituality
in those claiming not to be religious. The major reasons offered for
nonparticipation were time constraints, need to maintain appropriate boundaries
between physicians and patients, and fear of burnout.
CONCLUSION: Although many oncologists participate at least occasionally in some
sort of bereavement ritual, a significant proportion of oncologists are not
involved in these practices at all.
PMID: 20228130 [PubMed - indexed for MEDLINE]
9. Sarcoma. 2010;2010:927972. doi: 10.1155/2010/927972. Epub 2010 Mar 8.
Radiation therapy for palliation of sarcoma metastases: a unique and uniform
Soyfer V(1), Corn BW, Kollender Y, Tempelhoff H, Meller I, Merimsky O.
(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.
PMID: 20224682 [PubMed]
10. 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
Geva R(1), Jiveliouk I, Inbar M, Meller I, Friedman E, Merimsky O.
(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
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
PMID: 19194122 [PubMed - indexed for MEDLINE]
11. Oncology. 2009;76(1):30-5. doi: 10.1159/000178162. Epub 2008 Nov 26.
Ductal carcinoma in situ of the breast in Israeli women treated by
breast-conserving surgery followed by radiation therapy.
Jiveliouk I(1), Corn B, Inbar M, Merimsky O.
(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, affiliated with the
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
BACKGROUND: Lumpectomy followed by radiation therapy (RT) has become an accepted
local management strategy for patients with small, mammographically detected
ductal carcinoma in situ (DCIS) of the breast. The aim of this analysis is to
describe control rates and patterns of relapse in a cohort of Israeli women with
mammographically detected DCIS treated at a single medical center.
PATIENTS AND METHODS: The files of 107 consecutive patients with DCIS were
retrieved from the cancer registry of the unit of RT. All women underwent
lumpectomy followed by definitive RT, administered in conventional dose
fractionation regimens. Oral tamoxifen, 20 mg/ day, was prescribed to all but 2
patients with positive receptors.
RESULTS: Within a median follow-up time of 52 months, no local recurrence of any
breast tumor was found. There was no correlation between event-free survival and
tumor size, focality, grading, hormone receptor status, administration of
adjuvant hormonal therapy, timing of RT, and RT boost delivery. The 8-year
overall survival, disease-free-survival, and event-free survival were 100, 100,
and 87%, respectively.
CONCLUSIONS: The results reported herein are consistent with short-term and
intermediate-term outcomes that are better than the reported benchmarks from
prospective randomized trials. Although this could reflect selection factors at a
single institution, it is also plausible that a genetically distinct disease is
present in this local population.
PMID: 19033713 [PubMed - indexed for MEDLINE]
12. Anticancer Res. 2008 Sep-Oct;28(5B):3147-52.
Invasive breast cancer treated with taxol and epirubicin neo-adjuvant
chemotherapy: the role in the outcome of the "crosstalk" between Erb receptors
Sarid D(1), Ron IG, Shoshan L, Barnea I, Shina S, Baratz M, Greenberg J, Merimsky
O, Ben-Yosef R, Lev-Ari S, Keidar Y, Yaal-Hahoshen N.
(1)Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
PURPOSE: To correlate p53 and ErbB receptors status with disease-free survival
(DFS) and overall survival (OS) in locally advanced breast cancer.
PATIENTS AND METHODS: Sixty patients were included in a single-center,
open-label, phase II trial (1998-2003). Analysis of Erb receptors and p53 status
and estrogen receptor/progesterone receptor data were available for 33 patients.
Neoadjuvant epirubicin 75 mg/m2 and paclitaxel 175-200 mg/m2 were administered
every 21 days. The patients underwent surgery and radiation therapy and adjuvant
RESULTS: Approximately two thirds of the patients demonstrated overexpression of
ErbB receptors and had mutant p53 overexpression. The disease recurred in 11/33
patients and 7 died (median follow-up 56 months). Detrimental effects on OS were
established in cases of combined defective p53 expression and ErbB1-ErbB3
heterodimeric receptor overexpression. In contrast, normal p53 together with the
same overexpressed heterodimeric combination of ErbB receptors showed no
statistically significant effect.
CONCLUSION: In terms of the clinical impact of combinations of ErbB receptors
with or without mutant p53, only the overexpressed various ErbB1-ErbB3 dimeric
combinations and the ErbB1/ErbB2/ErbB3 triplet combination with mutated p53 were
related to a significantly poorer outcome. This observation may help in the
development of new strategies required for blocking these molecular pathways and
improving the outcome of patients with locally advanced breast cancer.
PMID: 19031973 [PubMed - indexed for MEDLINE]
13. 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.
(1)Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv
University, Tel-Aviv, Israel.
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]
14. J Thorac Oncol. 2008 Sep;3(9):994-1002. doi: 10.1097/JTO.0b013e31818396cb.
Oral vinorelbine and cisplatin as induction chemotherapy and concomitant
chemo-radiotherapy in stage III non-small cell lung cancer: final results of an
international phase II trial.
Krzakowski M(1), Provencio M, Utracka-Hutka B, Villa E, Codes M, Kuten A, Henke
M, Lopez M, Bell D, Biti G, Merimsky O, Beorchia A, Riggi M, Caux NR, Pouget JC,
Dubray B, David P.
(1)Institut de Recherche Pierre Fabre, Boulogne Billancourt, France.
INTRODUCTION: Cisplatin in combination with vinorelbine has reported an optimal
activity/tolerance ratio when used in combination with radiotherapy in locally
advanced unresectable non-small cell lung cancer. The currently available oral
formulation of vinorelbine should be easier to use assuming a similar activity
profile. An international phase II trial with vinorelbine oral and cisplatin as
induction followed by oral vinorelbine and cisplatin with concomitant
radiotherapy was implemented to evaluate the efficacy in terms of objective
response (OR) following this combination as primary end point and duration or
response, progression-free survival, overall survival, and safety as secondary
MATERIAL AND METHODS: The study included patients between 18 and 75 years, with
histologically proven untreated locally advanced inoperable stage IIIA/IIIB
(supraclavicular lymph nodes and pleural effusion excluded) non-small cell lung
cancer, adequate bone marrow, hepatic and renal function, Karnofsky performance
status >/=80%. Patients were treated with oral vinorelbine 60 mg/m day 1,8 cycle
1 and 80 mg/m day 1,8 cycle 2 (if no grade 3-4 toxicity) and cisplatin 80 mg/m
day 1 every 3 weeks for 2 cycles as induction. Patients without progression
received oral vinorelbine 40 mg/m day 1, 8 and cisplatin 80 mg/m day 1 every 3
weeks for 2 more cycles with radiotherapy 66 Gy in 6.5 weeks.
RESULTS: Patient and disease characteristics (n = 54) included: median age 57
years; female sex 24%; stage IIIA 48% and IIIB 52%; Squamous carcinoma 59%,
Karnofsky performance status 100% (range, 80-100%) 50%, patients >/=5% weight
loss at baseline 7%. Relative dose intensities of oral vinorelbine/cisplatin were
86%/93% and 97%/98% at induction and in combination with radiotherapy,
respectively. Forty-one patients (76%) increased oral vinorelbine from 60 to 80
mg/m day during induction (reasons for nonescalation: hematological 7 patients,
nonhematological 2 patients, error 4 patients). After two cycles of chemotherapy
induction, the OR intent-to-treat in the 54 patients was 37%. Toxicities during
induction were as follows: Neutropenia G3-4 (28%), Febrile Neutropenia (7%),
nausea G3 (11%), vomiting G3-4 (9%), anorexia G3 (4%), diarrhea G4 (2%),
constipation G3 (2%). Forty-seven out of 54 (87%) patients received concomitant
chemo-radiotherapy.Median radiotherapy delivered dose was 66 Gy. Tolerance: 9% G3
Neutropenia; 4% G3 dysphagia/radiation; 2% G3 radiation dermatitis. Late
pulmonary fibrosis was reported in one patient (1.8%). One month after completion
of chemo-radiotherapy, the overall OR intent-to-treat in the 54 patients was 54%
(95% CI: 40-67%). With a median follow-up of 37 months (95% CI: 34-41) the median
progression-free survival and overall survival were: 12.5 (95% CI: 9.6-16.4) and
23.4 (95% CI: 17.6-29.8) months, respectively.
CONCLUSION: Oral vinorelbine in combination with cisplatin is an effective
combination in stage IIIA/IIIB patients. The excellent tolerance profile allowed
to complete concomitant chemo-radiotherapy in 87% of patients. Oral vinorelbine
in combination with cisplatin is a new and promising option that facilitates the
administration of concomitant chemo-radiotherapy with high rates of treatment
PMID: 18758302 [PubMed - indexed for MEDLINE]
15. 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.
(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
PMID: 18521256 [PubMed]
16. 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.
(1)National Unit of Orthopedic Oncology, Tel-Aviv Sourasky Medical Center,
affiliated with Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 64239,
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]
17. Gynecol Obstet Invest. 2008;65(2):89-95. Epub 2007 Sep 18.
The complexity of management of pregnancy-associated malignant soft tissue and
Molho RB(1), Kollender Y, Issakov J, Bickels J, Flusser G, Azem F, Alon A, Inbar
MJ, Meller I, Merimsky O.
(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
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]
18. Harefuah. 2007 May;146(5):329-34, 408.
[Imatinib mesylate (glivec) as a treatment for gastrointestinal stromal tumor
(GIST)--long term follow-up].
[Article in Hebrew]
Raccah E(1), Merimsky O, Kuten A, Apter S, Catane R.
(1)Tel Aviv University, Tel Aviv.
BACKGROUND: Gastrointestinal stromal tumor (GIST) is a rare gastrointestinal
tumor. It is known to be resistant to radiotherapy and chemotherapy. The
administration of imatinib mesylate, a tyrosine kinase inhibitor, resulted in a
dramatic response and improved survival in patients with GIST. This study
examined the long term response and side effects of imatinib treatment in Israeli
patients with GIST.
PATIENTS AND METHODS: The study followed-up on 25 patients from various hospitals
in Israel treated between the years 2001 and 2006. The mean follow-up time was
36.3 months (17-63 months).
RESULTS: One patient achieved complete response, 13 patients (52%) achieved
partial response, 9 patients (35%) achieved stable disease, and 2 patients did
not have measurable disease. The median survival was not yet reached. Twelve
patients (48%) had a decrease in the attenuation of the tumor into a cystic
appearance. Eleven patients (44%) developed late resistance to the treatment
(after 7-54 months). The median time to progression was not yet reached. The
adverse events were mostly mild. Severe adverse events (grade 3-4 Common Toxicity
Criteria (CTC)) occurred in 24% of the patients. There was no advantage regarding
survival or time to progression for the patients who had partial response
compared to those patients who had stable disease (P=0.39 and P=0.71
CONCLUSIONS: Imatinib results in a dramatic response in patients with GIST, and
is well tolerated. The introduction of new drugs such as sunitinib which is now
in an advanced phase of clinical study, may provide additional solutions in the
treatment of GIST.
PMID: 17674545 [PubMed - indexed for MEDLINE]
19. J Bone Joint Surg Br. 2006 Dec;88(12):1647-51.
Liposarcoma in adult limbs treated by limb-sparing surgery and adjuvant
Issakov J(1), Soyfer V, Kollender Y, Bickels J, Meller I, Merimsky O.
(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]
20. 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.
(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
PMID: 16300847 [PubMed - indexed for MEDLINE]
21. 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.
(1)Unit of Musculoskeletal Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv,
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]
22. Int J Clin Oncol. 2004 Jun;9(3):202-5.
Cutaneous and subcutaneous metastases of rectal cancer.
Sarid D(1), Wigler N, Gutkin Z, Merimsky O, Leider-Trejo L, Ron IG.
(1)Department of Oncology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street,
Tel Aviv 64239, Israel.
The occurrence of cutaneous metastatic disease from colorectal cancer is uncommon
and typically signifies widespread disease with poor prognosis. Colorectal
metastases usually occur within the first 3 years of follow up, and the median
survival of patients after the appearance of cutaneous metastatic lesions is 18
to 20 months. We describe an unusual case of a 60-year-old woman with a
metachronous skin lesion as the sole site of metastatic disease, and a relatively
long interval between the appearance of skin metastases and death. The woman was
found to have an adenocarcinoma of the rectum, a Dukes' C lesion, extending over
the entire rectal wall into the perirectal fat; five of eight regional lymph
nodes showed metastases. Adjuvant radiotherapy followed by chemotherapy was
administered for about 1 year. A subcutaneous lump on the left abdominal wall
found 16 months postoperatively was metastatic of rectal origin. A metastatic
adenocarcinoma of rectal origin was found in a single left lower axillary node 26
months later. Despite metastatic work-up for the next 2 years, an enlarged and
palpated metastatic left inguinal lymph node appeared and was subjected to
radiation. Computerized tomography (CT) examination 5 years after the first
presentation of the rectal tumor and almost 4 years after the diagnosis of
abdominal skin metastases disclosed recurrent pelvic disease with severe left
hydronephrosis. Treatment by systemic chemotherapy was partially successful, but
she died 8 months after this chemotherapy was initiated.
PMID: 15221607 [PubMed - indexed for MEDLINE]
23. 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,
(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
PMID: 15050325 [PubMed - indexed for MEDLINE]
24. Gynecol Oncol. 2004 Apr;93(1):263-5.
Successful transfer of frozen-thawed embryos obtained after subtotal colectomy
for colorectal cancer and before fluorouracil-based chemotherapy.
Azem F(1), Amit A, Merimsky O, Lessing JB.
(1)The Sara Racine IVF Unit, Tel Aviv Sourasky Medical Center, Lis Maternity
Hospital, Tel Aviv, Israel.
Background. Fertility preservation is applied to patients with cancer who may be
rendered sterile from chemotherapy or radiotherapy. Fluorouracil is considered as
having almost no effect on human reproductive function, although clinical data
defining infertility risk is negligible. Case. Controlled ovarian stimulation, in
vitro fertilization (IVF), and embryo freezing were performed before
fluorouracil-based chemotherapy in a 28-year-old woman who underwent subtotal
colectomy for colorectal cancer (CRC). Three years later, when the clinical and
hormonal analysis confirmed ovarian failure, two thawed embryos were transferred
to the uterus. She gave birth at term to a 3200g infant. Discussion. Women with
good prognosis who wish to bear children in the future should be offered
fertility preservation options before chemotherapy, even if the likelihood of
permanent ovarian failure appears to be negligible.
PMID: 15047249 [PubMed - indexed for MEDLINE]
25. 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.
(1)Unit of Soft Tissue and Bone Oncology, Tel Aviv Sourasky Medical Center, Tel
PMID: 14740508 [PubMed - indexed for MEDLINE]
26. Radiother Oncol. 2003 Sep;68(3):289-94.
Comparison between two iodine-125 brachytherapy implant techniques: pre-planning
and intra-operative by various dosimetry quality indicators.
Matzkin H(1), Kaver I, Bramante-Schreiber L, Agai R, Merimsky O, Inbar M.
(1)Department of Urology, Sourasky Tel Aviv Medical Center, Tel Aviv University,
6 Weizmann Street, Tel Aviv 64329, Israel.
PURPOSE: To prospectively compare two widely used seed implant techniques:
pre-planning and intra-operative planning, based on 1 month post-implant CT-based
METHODS: We report results of a detailed 1 month post-operative dosimetric
evaluation and comparison between 142 consecutive men with prostate
adenocarcinoma treated by the pre-planning methodology and 214 men treated with
the real-time, intra-operative seed implant method.
RESULTS: Baseline parameters patient's age, Gleason score, clinical stage, and
gland volume were similar in both groups (p>0.05). Length of physicist time and
operating room team time were more than double in the pre-planned group compared
to the intra-operative one (205 vs 100 min). Based on day 30 post-implant CT, for
patients treated with the pre-planning method, mean V90, V100 and V150 (percent
prostate volume receiving 90, 100 and 150% of the prescribed dose) were 67.5,
58.35 and 21.5%, respectively, while for the intra-operative group they were
97.9, 95.2 and 45%, respectively (p<0.01). Mean D90, expressed as percent of
target matched peripheral dose (minimal dose covering 90% of the gland volume)
was 53% for the pre-planned group and 114% for the intra-operative group of men
(p<0.01). Short-term morbidity was minimal in both groups and did not correlate
with the technique employed.
CONCLUSIONS: This large-scale comparison of implant adequacy favours real-time
intra-operative method. While all dosimetric parameters are significantly better
with this method, no increased early morbidity was noted. Longer-term PSA-based
clinical outcome should substantiate our contention of the superiority of the
intra-operative method when compared to the pre-planning one.
PMID: 13129637 [PubMed - indexed for MEDLINE]
27. 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.
(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
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
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]
28. Rheumatology (Oxford). 2002 Oct;41(10):1113-8.
The use of surgery and yttrium 90 in the management of extensive and diffuse
pigmented villonodular synovitis of large joints.
Shabat S(1), Kollender Y, Merimsky O, Isakov J, Flusser G, Nyska M, Meller I.
(1)The National Unit of Orthopaedic Oncology, Sapir Medical Center, Kfar-Saba,
OBJECTIVE: The surgical treatment of extensive diffuse pigmented villonodular
synovitis (PVNS) of large joints alone is unsatisfactory, with high rates of
local recurrence. Post-synovectomy adjuvant treatment with external beam
radiation therapy or intra-articular injection of yttrium 90 (90Y) yielded better
results. We report our experience with 10 cases treated with debulking surgery
followed by intra-articular injection of 90Y.
PATIENTS AND METHODS: Between January 1989 and June 1998, 10 patients (eight
males and two females aged 15-49 yr) with extensive diffuse PVNS were treated. In
six patients the knee joint, in three patients the ankle joint, and in one
patient the hip joint were involved. The 10 patients underwent 15 operations, one
patient had three surgical procedures, and three patients underwent two surgeries
(the intervals between re-operations for local recurrence were 2-4 yr). All
patients had an intra-articular injection of 15-25 mCi (555-925 MBq) 90Y, 6-8
weeks after the last surgery.
RESULTS: Mean follow-up time was 6 yr (range 2.5-12 yr). All patients were
followed using repeated computerized tomography (CT) scans, magnetic resonance
imaging (MRI), plain X-ray films and bone scans semi-annually. In nine patients,
neither evidence of disease nor progression of bone or articular destruction were
noted. In one patient, stabilization of disease was achieved with no further
evidence of bony or articular damage. No complications were noticed after surgery
or after the intra-articular 90Y injection.
CONCLUSION: A combination of debulking surgery with intra-articular injection of
90Y for extensive diffuse PVNS of major joints is a reliable treatment method,
with good results.
PMID: 12364629 [PubMed - indexed for MEDLINE]
29. Eur J Cancer. 2002 Jul;38(10):1335-42.
ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of
Merimsky O(1), Issakov J, Bickels J, Kollender Y, Flusser G, Soyfer V, Schwartz
I, Inbar M, Meller I.
(1)Department of Oncology, The Tel-Aviv Sourasky Medical Center, 6 Weizman
ErbB-4 is a recently described growth factor receptor. Relatively little is known
about its expression in human tumours. In this study, we assessed the possible
role of erbB-4 as a tissue marker for soft-tissue sarcomas (STS) and its
correlation with the response to chemotherapy. The histological specimen of 29
patients with STS of a limb who had received preoperative doxorubicin (ADR)-based
chemotherapy were studied for the degree of necrosis and the expression of erbB-4
(by an avidin-biotin-peroxidase technique). ErbB-4 expression in the preoperative
tissue samples was compared with the expression in the postchemotherapy resected
tumour. The true objective response rate to preoperative chemotherapy was 34%.
Wide resection of the tumour was done in 12 patients, marginal in 14, amputation
in 2 and no surgery in 1. The tumour necrosis was above 90% in 9 patients, 60-90%
in 12, and less than 60% in 7 patients. An increase in erbB-4 expression was more
common in cases with no response to chemotherapy, while no change or a decrease
in erbB-4 was more common in responsive tumours (P=0.004). No correlation could
be found between the degree of necrosis or the chemotherapeutic regimen and the
change in expression of erbB-4. The median disease-free survival (DFS) was longer
for patients with a decrease or no change in expression of erbB-4 than for
patients with increased expression. It is believed that postchemotherapy new
expression or no downregulation of the erbB-4 molecule represents tumour
aggressiveness and increased capability of growth and spread.
PMID: 12091063 [PubMed - indexed for MEDLINE]