טיפול קרינתי

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.

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]

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.

Author information:

(1)Department of Oncology, Institute of Oncology, Sheba Medical Center, Tel

Hashomer, 52621, Ramat Gan, Israel, bar.jair@gmail.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

cancer patients.

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

first-line therapy.

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

received.

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.

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]

4. Lancet Oncol. 2014 Jan;15(1):59-68. doi: 10.1016/S1470-2045(13)70510-2. Epub 2013

Dec 9.

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,

Wehler T.

Comment in

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

chemoradiation.

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,

number NCT00409188.

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

between groups.

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).

PMID: 24331154 [PubMed - indexed for MEDLINE]

5. 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]

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.

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]

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.

Author information:

(1)Division of Oncology, Tel Aviv Medical Center, Tel-Aviv 64239, Israel.

oferm@tasmc.health.gov.il

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

Mar 12.

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.

Author information:

(1)bencorn@tasmc.health.gov.il

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.

PMCID: PMC3227959

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

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]

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

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]

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.

Author information:

(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

and p53.

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.

Author information:

(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

chemo/hormonotherapy.

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.

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]

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.

Author information:

(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

endpoints.

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

completion.

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.

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]

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.

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]

17. 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.

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.

Author information:

(1)Tel Aviv University, Tel Aviv. elirokah@walla.com

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

respectively).

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

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]

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.

Author information:

(1)Sackler School of Medicine, Tel-Aviv University, Israel.

oferm@tasmc.health.gov.il

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]

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.

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]

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.

Author information:

(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,

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.

merimsky@zahav.net.il

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]

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.

Author information:

(1)The Sara Racine IVF Unit, Tel Aviv Sourasky Medical Center, Lis Maternity

Hospital, Tel Aviv, Israel. azem@tasmc.health.gov.il

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.

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]

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.

Author information:

(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

evaluation.

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.

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.

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.

Author information:

(1)The National Unit of Orthopaedic Oncology, Sapir Medical Center, Kfar-Saba,

Israel.

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

neoadjuvant chemotherapy.

Merimsky O(1), Issakov J, Bickels J, Kollender Y, Flusser G, Soyfer V, Schwartz

I, Inbar M, Meller I.

Author information:

(1)Department of Oncology, The Tel-Aviv Sourasky Medical Center, 6 Weizman

Street, Israel. merimsky@sahav.net.il

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]

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