Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study

Background Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). Patients and Methods A multicentric retrospective...

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Veröffentlicht in:Annals of surgical oncology 2020-05, Vol.27 (5), p.1693-1699
Hauptverfasser: Neron, Mathias, Sajous, Christophe, Thezenas, Simon, Piperno-Neumann, Sophie, Reyal, Fabien, Laé, Marick, Chakiba, Camille, Penel, Nicolas, Ryckewaert, Thomas, Honoré, Charles, Bertucci, François, Monneur, Audrey, Salas, Sébastien, Duffaud, Florence, Saada-Bouzid, Esma, Isambert, Nicolas, Brahmi, Mehdi, Ray-Coquard, Isabelle, Blay, Jean-Yves, Firmin, Nelly
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container_end_page 1699
container_issue 5
container_start_page 1693
container_title Annals of surgical oncology
container_volume 27
creator Neron, Mathias
Sajous, Christophe
Thezenas, Simon
Piperno-Neumann, Sophie
Reyal, Fabien
Laé, Marick
Chakiba, Camille
Penel, Nicolas
Ryckewaert, Thomas
Honoré, Charles
Bertucci, François
Monneur, Audrey
Salas, Sébastien
Duffaud, Florence
Saada-Bouzid, Esma
Isambert, Nicolas
Brahmi, Mehdi
Ray-Coquard, Isabelle
Blay, Jean-Yves
Firmin, Nelly
description Background Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). Patients and Methods A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. Results 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31–80 months]. Median OS was 11.5 months (95% CI 7.5–18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27–6.19; p  = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14–0.78; p  = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone ( p  = 0.049). Conclusions The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.
doi_str_mv 10.1245/s10434-019-08097-x
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The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). Patients and Methods A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. Results 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31–80 months]. Median OS was 11.5 months (95% CI 7.5–18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27–6.19; p  = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14–0.78; p  = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone ( p  = 0.049). Conclusions The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-019-08097-x</identifier><identifier>PMID: 31773519</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Alkylating agents ; Alkylating Agents - therapeutic use ; Anthracycline ; Breast Neoplasms - mortality ; Breast Neoplasms - therapy ; Breast Oncology ; Cellular Biology ; Chemotherapy ; Chemotherapy, Adjuvant ; Female ; France - epidemiology ; Humans ; Life Sciences ; Male ; Medical prognosis ; Medicine ; Medicine &amp; Public Health ; Metastases ; Metastasis ; Middle Aged ; Multivariate analysis ; Neoplasm Metastasis - therapy ; Oncology ; Patients ; Phyllodes Tumor - mortality ; Phyllodes Tumor - therapy ; Prognosis ; Radiation therapy ; Retrospective Studies ; Sarcoma ; Surgery ; Surgical Oncology ; Surgical Procedures, Operative ; Survival ; Survival Analysis ; Tumors ; Young Adult</subject><ispartof>Annals of surgical oncology, 2020-05, Vol.27 (5), p.1693-1699</ispartof><rights>Society of Surgical Oncology 2019</rights><rights>Society of Surgical Oncology 2019.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-ada253268ec72864e0029fc49c1c9c908d61c504eac6caa29ec7ab8b0a33ca193</citedby><cites>FETCH-LOGICAL-c409t-ada253268ec72864e0029fc49c1c9c908d61c504eac6caa29ec7ab8b0a33ca193</cites><orcidid>0000-0002-0007-5913 ; 0000-0001-5243-1548 ; 0000-0001-5839-6261 ; 0000-0002-0157-0959 ; 0000-0001-7190-120X ; 0000-0003-2472-1219 ; 0000-0003-2472-8306</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1245/s10434-019-08097-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1245/s10434-019-08097-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31773519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02530556$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Neron, Mathias</creatorcontrib><creatorcontrib>Sajous, Christophe</creatorcontrib><creatorcontrib>Thezenas, Simon</creatorcontrib><creatorcontrib>Piperno-Neumann, Sophie</creatorcontrib><creatorcontrib>Reyal, Fabien</creatorcontrib><creatorcontrib>Laé, Marick</creatorcontrib><creatorcontrib>Chakiba, Camille</creatorcontrib><creatorcontrib>Penel, Nicolas</creatorcontrib><creatorcontrib>Ryckewaert, Thomas</creatorcontrib><creatorcontrib>Honoré, Charles</creatorcontrib><creatorcontrib>Bertucci, François</creatorcontrib><creatorcontrib>Monneur, Audrey</creatorcontrib><creatorcontrib>Salas, Sébastien</creatorcontrib><creatorcontrib>Duffaud, Florence</creatorcontrib><creatorcontrib>Saada-Bouzid, Esma</creatorcontrib><creatorcontrib>Isambert, Nicolas</creatorcontrib><creatorcontrib>Brahmi, Mehdi</creatorcontrib><creatorcontrib>Ray-Coquard, Isabelle</creatorcontrib><creatorcontrib>Blay, Jean-Yves</creatorcontrib><creatorcontrib>Firmin, Nelly</creatorcontrib><creatorcontrib>French Sarcoma Group (GSF-GETO)</creatorcontrib><creatorcontrib>The French Sarcoma Group (GSF-GETO)</creatorcontrib><title>Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Background Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). Patients and Methods A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. Results 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31–80 months]. Median OS was 11.5 months (95% CI 7.5–18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27–6.19; p  = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14–0.78; p  = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone ( p  = 0.049). Conclusions The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alkylating agents</subject><subject>Alkylating Agents - therapeutic use</subject><subject>Anthracycline</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - therapy</subject><subject>Breast Oncology</subject><subject>Cellular Biology</subject><subject>Chemotherapy</subject><subject>Chemotherapy, Adjuvant</subject><subject>Female</subject><subject>France - epidemiology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Neoplasm Metastasis - therapy</subject><subject>Oncology</subject><subject>Patients</subject><subject>Phyllodes Tumor - mortality</subject><subject>Phyllodes Tumor - therapy</subject><subject>Prognosis</subject><subject>Radiation therapy</subject><subject>Retrospective Studies</subject><subject>Sarcoma</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Surgical Procedures, Operative</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kc1u1DAURi0EoqXwAiyQJVYsDP5LYrMLI6CVZlREy9q643hmUpI42E7VvEsfti4phRWSJVvX555r60PoNaPvGZfFh8ioFJJQpglVVFfk5gk6ZkUuyVKxp_lMS0U0L4sj9CLGK0pZJWjxHB0JVlWiYPoY3Z71I9iE_Q5vXIKYVxvxxRT2LswYhgbX3c-5g9QOe1Lv3ZDIJ4iuwauD6306uADjjP2Az6dkfe_iP6bUWryBrt0PMCT87TB3nW8ycTn1PsSPuMabqctQlrqAv7sUfBydTe21wxdpauaX6NkOuuhePewn6MeXz5erU7I-_3q2qtfESqoTgQZ4IXipnK24KqWjlOudldoyq62mqimZLah0YEsLwHXmYKu2FISwwLQ4Qe8W7wE6M4a2hzAbD605rdfmvkaznxZFec0y-3Zhx-B_TS4mc-WnMOTnGS5UxSRXXGaKL5TNf4rB7R61jJr78MwSnsnhmd_hmZvc9OZBPW171zy2_EkrA2IBYr4ackJ_Z_9Hewf4VKfw</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Neron, Mathias</creator><creator>Sajous, Christophe</creator><creator>Thezenas, Simon</creator><creator>Piperno-Neumann, Sophie</creator><creator>Reyal, Fabien</creator><creator>Laé, Marick</creator><creator>Chakiba, Camille</creator><creator>Penel, Nicolas</creator><creator>Ryckewaert, Thomas</creator><creator>Honoré, Charles</creator><creator>Bertucci, François</creator><creator>Monneur, Audrey</creator><creator>Salas, Sébastien</creator><creator>Duffaud, Florence</creator><creator>Saada-Bouzid, Esma</creator><creator>Isambert, Nicolas</creator><creator>Brahmi, Mehdi</creator><creator>Ray-Coquard, Isabelle</creator><creator>Blay, Jean-Yves</creator><creator>Firmin, Nelly</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-0007-5913</orcidid><orcidid>https://orcid.org/0000-0001-5243-1548</orcidid><orcidid>https://orcid.org/0000-0001-5839-6261</orcidid><orcidid>https://orcid.org/0000-0002-0157-0959</orcidid><orcidid>https://orcid.org/0000-0001-7190-120X</orcidid><orcidid>https://orcid.org/0000-0003-2472-1219</orcidid><orcidid>https://orcid.org/0000-0003-2472-8306</orcidid></search><sort><creationdate>20200501</creationdate><title>Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study</title><author>Neron, Mathias ; Sajous, Christophe ; Thezenas, Simon ; Piperno-Neumann, Sophie ; Reyal, Fabien ; Laé, Marick ; Chakiba, Camille ; Penel, Nicolas ; Ryckewaert, Thomas ; Honoré, Charles ; Bertucci, François ; Monneur, Audrey ; Salas, Sébastien ; Duffaud, Florence ; Saada-Bouzid, Esma ; Isambert, Nicolas ; Brahmi, Mehdi ; Ray-Coquard, Isabelle ; Blay, Jean-Yves ; Firmin, Nelly</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-ada253268ec72864e0029fc49c1c9c908d61c504eac6caa29ec7ab8b0a33ca193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alkylating agents</topic><topic>Alkylating Agents - therapeutic use</topic><topic>Anthracycline</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - therapy</topic><topic>Breast Oncology</topic><topic>Cellular Biology</topic><topic>Chemotherapy</topic><topic>Chemotherapy, Adjuvant</topic><topic>Female</topic><topic>France - epidemiology</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Neoplasm Metastasis - therapy</topic><topic>Oncology</topic><topic>Patients</topic><topic>Phyllodes Tumor - mortality</topic><topic>Phyllodes Tumor - therapy</topic><topic>Prognosis</topic><topic>Radiation therapy</topic><topic>Retrospective Studies</topic><topic>Sarcoma</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Surgical Procedures, Operative</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Neron, Mathias</creatorcontrib><creatorcontrib>Sajous, Christophe</creatorcontrib><creatorcontrib>Thezenas, Simon</creatorcontrib><creatorcontrib>Piperno-Neumann, Sophie</creatorcontrib><creatorcontrib>Reyal, Fabien</creatorcontrib><creatorcontrib>Laé, Marick</creatorcontrib><creatorcontrib>Chakiba, Camille</creatorcontrib><creatorcontrib>Penel, Nicolas</creatorcontrib><creatorcontrib>Ryckewaert, Thomas</creatorcontrib><creatorcontrib>Honoré, Charles</creatorcontrib><creatorcontrib>Bertucci, François</creatorcontrib><creatorcontrib>Monneur, Audrey</creatorcontrib><creatorcontrib>Salas, Sébastien</creatorcontrib><creatorcontrib>Duffaud, Florence</creatorcontrib><creatorcontrib>Saada-Bouzid, Esma</creatorcontrib><creatorcontrib>Isambert, Nicolas</creatorcontrib><creatorcontrib>Brahmi, Mehdi</creatorcontrib><creatorcontrib>Ray-Coquard, Isabelle</creatorcontrib><creatorcontrib>Blay, Jean-Yves</creatorcontrib><creatorcontrib>Firmin, Nelly</creatorcontrib><creatorcontrib>French Sarcoma Group (GSF-GETO)</creatorcontrib><creatorcontrib>The French Sarcoma Group (GSF-GETO)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; 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The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). Patients and Methods A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. Results 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31–80 months]. Median OS was 11.5 months (95% CI 7.5–18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27–6.19; p  = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14–0.78; p  = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone ( p  = 0.049). Conclusions The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>31773519</pmid><doi>10.1245/s10434-019-08097-x</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-0007-5913</orcidid><orcidid>https://orcid.org/0000-0001-5243-1548</orcidid><orcidid>https://orcid.org/0000-0001-5839-6261</orcidid><orcidid>https://orcid.org/0000-0002-0157-0959</orcidid><orcidid>https://orcid.org/0000-0001-7190-120X</orcidid><orcidid>https://orcid.org/0000-0003-2472-1219</orcidid><orcidid>https://orcid.org/0000-0003-2472-8306</orcidid></addata></record>
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identifier ISSN: 1068-9265
ispartof Annals of surgical oncology, 2020-05, Vol.27 (5), p.1693-1699
issn 1068-9265
1534-4681
language eng
recordid cdi_hal_primary_oai_HAL_hal_02530556v1
source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Adult
Aged
Aged, 80 and over
Alkylating agents
Alkylating Agents - therapeutic use
Anthracycline
Breast Neoplasms - mortality
Breast Neoplasms - therapy
Breast Oncology
Cellular Biology
Chemotherapy
Chemotherapy, Adjuvant
Female
France - epidemiology
Humans
Life Sciences
Male
Medical prognosis
Medicine
Medicine & Public Health
Metastases
Metastasis
Middle Aged
Multivariate analysis
Neoplasm Metastasis - therapy
Oncology
Patients
Phyllodes Tumor - mortality
Phyllodes Tumor - therapy
Prognosis
Radiation therapy
Retrospective Studies
Sarcoma
Surgery
Surgical Oncology
Surgical Procedures, Operative
Survival
Survival Analysis
Tumors
Young Adult
title Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study
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