Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer
•Pre-treatment bicarbonate is associated with tumor recurrence after lung SBRT.•This remained after accounting for dose, T-stage, tumor volume, and histology.•Findings were validated in an independent cohort from three institutions. Tumor aggressiveness and hypoxia are linked to acidosis in the tumo...
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| Veröffentlicht in: | Radiotherapy and oncology 2019-11, Vol.140, p.26-33 |
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| creator | Sebastian, Nikhil Wu, Trudy Driscoll, Erin Willers, Henning Kelly, Suzanne Musunuru, Hima Bindu Mo, Xiaokui Tan, Yubo Bazan, Jose Haglund, Karl Xu-Welliver, Meng Baschnagel, Andrew M. Ju, Andrew Keane, Florence Williams, Terence M. |
| description | •Pre-treatment bicarbonate is associated with tumor recurrence after lung SBRT.•This remained after accounting for dose, T-stage, tumor volume, and histology.•Findings were validated in an independent cohort from three institutions.
Tumor aggressiveness and hypoxia are linked to acidosis in the tumor microenvironment (TME). We hypothesized that low pre-treatment serum bicarbonate, potentially correlating with an acidic and hypoxic TME, predicts for poor outcomes after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC).
We included patients with localized NSCLC treated to a biologically effective dose (BED) ≥ 100 Gy, with available pre-treatment bicarbonate values within 3 months of treatment. We used receiver operating characteristic analysis to determine the bicarbonate concentration optimally predicting for primary tumor recurrence, and evaluated its association with recurrence and survival. We validated our findings in an independent cohort of patients from three collaborating institutions.
A total of 110 patients and 114 tumors were included in the training cohort, with median follow-up of 15.0 months. Bicarbonate |
| doi_str_mv | 10.1016/j.radonc.2019.05.014 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7080525</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0167814019329159</els_id><sourcerecordid>2242166137</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-3b94561ac79939a268e02029851c23d721cae1b87aec846382a24a741fd8f0473</originalsourceid><addsrcrecordid>eNp9UU2P1DAMrRCInV34BwjlyKUlST-SXpDQClikleAA58h13Z2M2mRI0kXDz-GXktEMC1y4OLJjv-fnVxQvBK8EF93rXRVg9A4ryUVf8bbionlUbIRWfcm1Vo-LTW5TpRYNvyguY9xxziWv1dPiohZCdZJ3m-Ln50BlCgRpIZdYpLAubLAIYfAOErF9oNFiimzyISd2gXBgaV1yht6l4GcGU6LAYg7kE2CyyAY_Hljez0Ky3rG0pQD7A7OO7XMlM0X23aYtmz3CbH_QyJx3ZVxgnhlSDvPq7hiCQwrPiicTzJGen9-r4uv7d1-ub8rbTx8-Xr-9LbHp6lTWQ9-0nQBUfV_3IDtNWa7sdStQ1qOSAoHEoBUQ6jyhJcgGVCOmUU-8UfVV8eaEu1-HhUbMWwaYzVmz8WDNvz_Obs2dvzeKa97KNgO8OgME_22lmMxi41ENOPJrNFI2UnSdqI9czakVg48x0PRAI7g52mt25mSvOdpreGuyvXns5d8rPgz99vOPBsqHurcUTMR8bsweBsJkRm__z_ALXwy9fQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2242166137</pqid></control><display><type>article</type><title>Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Sebastian, Nikhil ; Wu, Trudy ; Driscoll, Erin ; Willers, Henning ; Kelly, Suzanne ; Musunuru, Hima Bindu ; Mo, Xiaokui ; Tan, Yubo ; Bazan, Jose ; Haglund, Karl ; Xu-Welliver, Meng ; Baschnagel, Andrew M. ; Ju, Andrew ; Keane, Florence ; Williams, Terence M.</creator><creatorcontrib>Sebastian, Nikhil ; Wu, Trudy ; Driscoll, Erin ; Willers, Henning ; Kelly, Suzanne ; Musunuru, Hima Bindu ; Mo, Xiaokui ; Tan, Yubo ; Bazan, Jose ; Haglund, Karl ; Xu-Welliver, Meng ; Baschnagel, Andrew M. ; Ju, Andrew ; Keane, Florence ; Williams, Terence M.</creatorcontrib><description>•Pre-treatment bicarbonate is associated with tumor recurrence after lung SBRT.•This remained after accounting for dose, T-stage, tumor volume, and histology.•Findings were validated in an independent cohort from three institutions.
Tumor aggressiveness and hypoxia are linked to acidosis in the tumor microenvironment (TME). We hypothesized that low pre-treatment serum bicarbonate, potentially correlating with an acidic and hypoxic TME, predicts for poor outcomes after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC).
We included patients with localized NSCLC treated to a biologically effective dose (BED) ≥ 100 Gy, with available pre-treatment bicarbonate values within 3 months of treatment. We used receiver operating characteristic analysis to determine the bicarbonate concentration optimally predicting for primary tumor recurrence, and evaluated its association with recurrence and survival. We validated our findings in an independent cohort of patients from three collaborating institutions.
A total of 110 patients and 114 tumors were included in the training cohort, with median follow-up of 15.0 months. Bicarbonate < 26 mEq/L was associated with primary tumor recurrence on univariate (HR = 5.92; 95% CI 1.69–24.88; p = 0.005) and multivariate analysis (HR = 5.48; 95% CI 1.37–25.19; p = 0.020). The validation cohort consisted of 195 patients and 208 tumors with median follow-up of 27.5 months. In the validation cohort, bicarbonate < 26 mEq/L was again associated with primary tumor recurrence on univariate (HR = 3.38; 95% CI 1.27–9.37; p = 0.015) and multivariate analysis (HR = 3.33; 1.18–10.07; p = 0.023).
Pre-treatment bicarbonate predicts for primary tumor control in NSCLC treated with SBRT and may be useful for risk stratification. These findings should be confirmed prospectively.</description><identifier>ISSN: 0167-8140</identifier><identifier>ISSN: 1879-0887</identifier><identifier>EISSN: 1879-0887</identifier><identifier>DOI: 10.1016/j.radonc.2019.05.014</identifier><identifier>PMID: 31176206</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Aged ; Aged, 80 and over ; Bicarbonate ; Bicarbonates - blood ; Carcinoma, Non-Small-Cell Lung - blood ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - radiotherapy ; Female ; Humans ; Lung Neoplasms - blood ; Lung Neoplasms - mortality ; Lung Neoplasms - radiotherapy ; Male ; Middle Aged ; Non-small cell lung cancer ; Primary tumor recurrence ; Radiosurgery ; Stereotactic body radiation therapy ; Tumor Microenvironment</subject><ispartof>Radiotherapy and oncology, 2019-11, Vol.140, p.26-33</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-3b94561ac79939a268e02029851c23d721cae1b87aec846382a24a741fd8f0473</citedby><cites>FETCH-LOGICAL-c463t-3b94561ac79939a268e02029851c23d721cae1b87aec846382a24a741fd8f0473</cites><orcidid>0000-0002-3977-7867 ; 0000-0002-1020-0845</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.radonc.2019.05.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31176206$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sebastian, Nikhil</creatorcontrib><creatorcontrib>Wu, Trudy</creatorcontrib><creatorcontrib>Driscoll, Erin</creatorcontrib><creatorcontrib>Willers, Henning</creatorcontrib><creatorcontrib>Kelly, Suzanne</creatorcontrib><creatorcontrib>Musunuru, Hima Bindu</creatorcontrib><creatorcontrib>Mo, Xiaokui</creatorcontrib><creatorcontrib>Tan, Yubo</creatorcontrib><creatorcontrib>Bazan, Jose</creatorcontrib><creatorcontrib>Haglund, Karl</creatorcontrib><creatorcontrib>Xu-Welliver, Meng</creatorcontrib><creatorcontrib>Baschnagel, Andrew M.</creatorcontrib><creatorcontrib>Ju, Andrew</creatorcontrib><creatorcontrib>Keane, Florence</creatorcontrib><creatorcontrib>Williams, Terence M.</creatorcontrib><title>Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer</title><title>Radiotherapy and oncology</title><addtitle>Radiother Oncol</addtitle><description>•Pre-treatment bicarbonate is associated with tumor recurrence after lung SBRT.•This remained after accounting for dose, T-stage, tumor volume, and histology.•Findings were validated in an independent cohort from three institutions.
Tumor aggressiveness and hypoxia are linked to acidosis in the tumor microenvironment (TME). We hypothesized that low pre-treatment serum bicarbonate, potentially correlating with an acidic and hypoxic TME, predicts for poor outcomes after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC).
We included patients with localized NSCLC treated to a biologically effective dose (BED) ≥ 100 Gy, with available pre-treatment bicarbonate values within 3 months of treatment. We used receiver operating characteristic analysis to determine the bicarbonate concentration optimally predicting for primary tumor recurrence, and evaluated its association with recurrence and survival. We validated our findings in an independent cohort of patients from three collaborating institutions.
A total of 110 patients and 114 tumors were included in the training cohort, with median follow-up of 15.0 months. Bicarbonate < 26 mEq/L was associated with primary tumor recurrence on univariate (HR = 5.92; 95% CI 1.69–24.88; p = 0.005) and multivariate analysis (HR = 5.48; 95% CI 1.37–25.19; p = 0.020). The validation cohort consisted of 195 patients and 208 tumors with median follow-up of 27.5 months. In the validation cohort, bicarbonate < 26 mEq/L was again associated with primary tumor recurrence on univariate (HR = 3.38; 95% CI 1.27–9.37; p = 0.015) and multivariate analysis (HR = 3.33; 1.18–10.07; p = 0.023).
Pre-treatment bicarbonate predicts for primary tumor control in NSCLC treated with SBRT and may be useful for risk stratification. These findings should be confirmed prospectively.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Bicarbonate</subject><subject>Bicarbonates - blood</subject><subject>Carcinoma, Non-Small-Cell Lung - blood</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - radiotherapy</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - blood</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - radiotherapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Non-small cell lung cancer</subject><subject>Primary tumor recurrence</subject><subject>Radiosurgery</subject><subject>Stereotactic body radiation therapy</subject><subject>Tumor Microenvironment</subject><issn>0167-8140</issn><issn>1879-0887</issn><issn>1879-0887</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU2P1DAMrRCInV34BwjlyKUlST-SXpDQClikleAA58h13Z2M2mRI0kXDz-GXktEMC1y4OLJjv-fnVxQvBK8EF93rXRVg9A4ryUVf8bbionlUbIRWfcm1Vo-LTW5TpRYNvyguY9xxziWv1dPiohZCdZJ3m-Ln50BlCgRpIZdYpLAubLAIYfAOErF9oNFiimzyISd2gXBgaV1yht6l4GcGU6LAYg7kE2CyyAY_Hljez0Ky3rG0pQD7A7OO7XMlM0X23aYtmz3CbH_QyJx3ZVxgnhlSDvPq7hiCQwrPiicTzJGen9-r4uv7d1-ub8rbTx8-Xr-9LbHp6lTWQ9-0nQBUfV_3IDtNWa7sdStQ1qOSAoHEoBUQ6jyhJcgGVCOmUU-8UfVV8eaEu1-HhUbMWwaYzVmz8WDNvz_Obs2dvzeKa97KNgO8OgME_22lmMxi41ENOPJrNFI2UnSdqI9czakVg48x0PRAI7g52mt25mSvOdpreGuyvXns5d8rPgz99vOPBsqHurcUTMR8bsweBsJkRm__z_ALXwy9fQ</recordid><startdate>20191101</startdate><enddate>20191101</enddate><creator>Sebastian, Nikhil</creator><creator>Wu, Trudy</creator><creator>Driscoll, Erin</creator><creator>Willers, Henning</creator><creator>Kelly, Suzanne</creator><creator>Musunuru, Hima Bindu</creator><creator>Mo, Xiaokui</creator><creator>Tan, Yubo</creator><creator>Bazan, Jose</creator><creator>Haglund, Karl</creator><creator>Xu-Welliver, Meng</creator><creator>Baschnagel, Andrew M.</creator><creator>Ju, Andrew</creator><creator>Keane, Florence</creator><creator>Williams, Terence M.</creator><general>Elsevier B.V</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3977-7867</orcidid><orcidid>https://orcid.org/0000-0002-1020-0845</orcidid></search><sort><creationdate>20191101</creationdate><title>Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer</title><author>Sebastian, Nikhil ; Wu, Trudy ; Driscoll, Erin ; Willers, Henning ; Kelly, Suzanne ; Musunuru, Hima Bindu ; Mo, Xiaokui ; Tan, Yubo ; Bazan, Jose ; Haglund, Karl ; Xu-Welliver, Meng ; Baschnagel, Andrew M. ; Ju, Andrew ; Keane, Florence ; Williams, Terence M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-3b94561ac79939a268e02029851c23d721cae1b87aec846382a24a741fd8f0473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Bicarbonate</topic><topic>Bicarbonates - blood</topic><topic>Carcinoma, Non-Small-Cell Lung - blood</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - radiotherapy</topic><topic>Female</topic><topic>Humans</topic><topic>Lung Neoplasms - blood</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - radiotherapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Non-small cell lung cancer</topic><topic>Primary tumor recurrence</topic><topic>Radiosurgery</topic><topic>Stereotactic body radiation therapy</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sebastian, Nikhil</creatorcontrib><creatorcontrib>Wu, Trudy</creatorcontrib><creatorcontrib>Driscoll, Erin</creatorcontrib><creatorcontrib>Willers, Henning</creatorcontrib><creatorcontrib>Kelly, Suzanne</creatorcontrib><creatorcontrib>Musunuru, Hima Bindu</creatorcontrib><creatorcontrib>Mo, Xiaokui</creatorcontrib><creatorcontrib>Tan, Yubo</creatorcontrib><creatorcontrib>Bazan, Jose</creatorcontrib><creatorcontrib>Haglund, Karl</creatorcontrib><creatorcontrib>Xu-Welliver, Meng</creatorcontrib><creatorcontrib>Baschnagel, Andrew M.</creatorcontrib><creatorcontrib>Ju, Andrew</creatorcontrib><creatorcontrib>Keane, Florence</creatorcontrib><creatorcontrib>Williams, Terence M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Radiotherapy and oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sebastian, Nikhil</au><au>Wu, Trudy</au><au>Driscoll, Erin</au><au>Willers, Henning</au><au>Kelly, Suzanne</au><au>Musunuru, Hima Bindu</au><au>Mo, Xiaokui</au><au>Tan, Yubo</au><au>Bazan, Jose</au><au>Haglund, Karl</au><au>Xu-Welliver, Meng</au><au>Baschnagel, Andrew M.</au><au>Ju, Andrew</au><au>Keane, Florence</au><au>Williams, Terence M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer</atitle><jtitle>Radiotherapy and oncology</jtitle><addtitle>Radiother Oncol</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>140</volume><spage>26</spage><epage>33</epage><pages>26-33</pages><issn>0167-8140</issn><issn>1879-0887</issn><eissn>1879-0887</eissn><abstract>•Pre-treatment bicarbonate is associated with tumor recurrence after lung SBRT.•This remained after accounting for dose, T-stage, tumor volume, and histology.•Findings were validated in an independent cohort from three institutions.
Tumor aggressiveness and hypoxia are linked to acidosis in the tumor microenvironment (TME). We hypothesized that low pre-treatment serum bicarbonate, potentially correlating with an acidic and hypoxic TME, predicts for poor outcomes after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC).
We included patients with localized NSCLC treated to a biologically effective dose (BED) ≥ 100 Gy, with available pre-treatment bicarbonate values within 3 months of treatment. We used receiver operating characteristic analysis to determine the bicarbonate concentration optimally predicting for primary tumor recurrence, and evaluated its association with recurrence and survival. We validated our findings in an independent cohort of patients from three collaborating institutions.
A total of 110 patients and 114 tumors were included in the training cohort, with median follow-up of 15.0 months. Bicarbonate < 26 mEq/L was associated with primary tumor recurrence on univariate (HR = 5.92; 95% CI 1.69–24.88; p = 0.005) and multivariate analysis (HR = 5.48; 95% CI 1.37–25.19; p = 0.020). The validation cohort consisted of 195 patients and 208 tumors with median follow-up of 27.5 months. In the validation cohort, bicarbonate < 26 mEq/L was again associated with primary tumor recurrence on univariate (HR = 3.38; 95% CI 1.27–9.37; p = 0.015) and multivariate analysis (HR = 3.33; 1.18–10.07; p = 0.023).
Pre-treatment bicarbonate predicts for primary tumor control in NSCLC treated with SBRT and may be useful for risk stratification. These findings should be confirmed prospectively.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31176206</pmid><doi>10.1016/j.radonc.2019.05.014</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3977-7867</orcidid><orcidid>https://orcid.org/0000-0002-1020-0845</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Bicarbonate Bicarbonates - blood Carcinoma, Non-Small-Cell Lung - blood Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - radiotherapy Female Humans Lung Neoplasms - blood Lung Neoplasms - mortality Lung Neoplasms - radiotherapy Male Middle Aged Non-small cell lung cancer Primary tumor recurrence Radiosurgery Stereotactic body radiation therapy Tumor Microenvironment |
| title | Pre-treatment serum bicarbonate predicts for primary tumor control after stereotactic body radiation therapy in patients with localized non-small cell lung cancer |
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