Publications by authors named "William G Breen"

15 Publications

  • Page 1 of 1

Hippocampal Avoidance Prophylactic Cranial Irradiation for SCLC.

J Thorac Oncol 2021 06;16(6):e41-e42

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2021.02.019DOI Listing
June 2021

The prognostic value, sensitivity, and specificity of multiparametric magnetic resonance imaging before salvage radiotherapy for prostate cancer.

Radiother Oncol 2021 Aug 21;161:9-15. Epub 2021 May 21.

Department of Radiation Oncology, Mayo Clinic, Rochester, USA.

Aim: To determine the operational characteristics of pelvic magnetic resonance imaging (MRI) prior to salvage radiation therapy (SRT) for biochemically recurrent prostate cancer following radical prostatectomy.

Methods And Materials: We reviewed the medical records of 386 patients who underwent MRI prior to SRT. We assessed associations of pre-SRT MRI findings with biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and salvage androgen deprivation therapy (ADT) use following SRT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for detecting local recurrence were also calculated.

Results: Pre-SRT MRI was positive for local recurrence in 216 patients (56%), indeterminate in 46 (12%), and negative in 124 (32%). On univariate analysis, BCR following SRT was significantly less likely for patients with positive (HR: 0.58, 95% CI: 0.42-0.8) or indeterminate (HR: 0.6: 0.36-1) MRI findings, compared to patients with negative imaging (p = 0.003). These associations remained significant on multivariate analysis (p < 0.05) and across pre-SRT PSA groups. For the entire cohort, the sensitivity of MRI for local recurrence was 61.0% (53.5-68.1%), specificity 60.0% (44.3-73.0%), PPV 86.1% (78.9-91.5%) and NPV 27.6% (19.0-37.5%). Sensitivity of MRI was better in men with higher pre-SRT PSA (80.0% for PSA > 1.0), and specificity was improved with lower pre-SRT PSA (73.9% for PSA 0.1-0.5).

Conclusions: Positive or indeterminate MRI findings prior to SRT were associated with improved biochemical control following SRT, across PSA levels. The sensitivity and specificity of MRI for local recurrence were 61% and 58.7%, respectively.
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http://dx.doi.org/10.1016/j.radonc.2021.05.015DOI Listing
August 2021

Leptomeningeal disease and neurologic death after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis.

Adv Radiat Oncol 2021 Mar-Apr;6(2):100644. Epub 2021 Jan 8.

Department of Radiation Oncology, Stanford University, Stanford, California.

Purpose: Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described.

Methods And Materials: The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT.

Results: The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, = .92).

Conclusions: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation.
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http://dx.doi.org/10.1016/j.adro.2021.100644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940785PMC
January 2021

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience.

Clin Transl Radiat Oncol 2021 May 23;28:17-23. Epub 2021 Feb 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States.

Introduction: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC).

Materials And Methods: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs.

Results: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55-69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28-89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%-89%), 77% (95% CI: 68%-86%), and 78% (95% CI: 70%-86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%-9%), 9% (95% CI: 5%-17%), and 10% (95% CI: 6%-18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4-19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001).

Conclusions: IMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC.
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http://dx.doi.org/10.1016/j.ctro.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943964PMC
May 2021

Ablative radiotherapy for ultracentral lung cancers: Dosimetric, geometric, and volumetric predictors of outcomes and toxicity.

Radiother Oncol 2021 05 10;158:246-252. Epub 2021 Mar 10.

Department of Radiation Oncology, Mayo Clinic, Rochester, United States. Electronic address:

Background: Ultracentral lung cancers arise near the proximal bronchial tree (PBT), trachea, or esophagus, and have been associated with worse outcomes and increased toxicity after radiotherapy. We sought to associate dosimetric and anatomic factors with oncologic outcomes and toxicities.

Methods: One-hundred ten patients treated with ablative, curative-intent radiotherapy for ultracentral, node-negative, non-small cell lung cancer were included. Dosimetric and geometric data obtained using custom software that calculated volumes of target structures and organs-at-risk and measured the shortest vector length between these volumes were associated with outcomes and toxicity.

Results: Common dose/fractionation schemes included 50 Gy in 5 fractions (57%), 60 Gy in 8 fractions (15%), and 48 Gy in 4 fractions (13%). Overall survival at 1, 2, and 5 years was 78%, 57%, and 32%, respectively. Factors significantly associated with death included endobronchial tumor, gross tumor volume (GTV) or planning target volume (PTV) contacting PBT, shorter distance from GTV to PBT or esophagus, volume of PBT receiving prescription dose, higher pericardium max dose, lung V20Gy, and mean lung dose. Local progression at 1, 2, and 5 years was 4%, 16%, and 21%. Factors associated with local progression were lower GTV minimum dose and higher GTV/PTV volume ratio. Acute and late grade 2 + toxicity was seen in 18% and 27%, respectively. Four patients (4%) had fatal toxicity.

Conclusions: Lower GTV minimum dose and smaller volumetric PTV expansions may increase risk of local progression, and should be balanced against normal tissue doses including pericardium maximum dose, lung V20Gy, and mean lung dose.
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http://dx.doi.org/10.1016/j.radonc.2021.03.001DOI Listing
May 2021

Adjuvant brachytherapy for FIGO stage I serous or clear cell endometrial cancer.

Int J Gynecol Cancer 2021 Jun 9;31(6):859-867. Epub 2021 Feb 9.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: Optimal adjuvant treatment for early-stage clear cell and serous endometrial cancer remains unclear. We report outcomes for women with surgically staged International Federation of Gynecology and Obstetrics (FIGO) stage I clear cell, serous, and mixed endometrial cancers following adjuvant vaginal cuff brachytherapy with or without chemotherapy.

Methods: From April 1998 to January 2020, women with FIGO stage IA-IB clear cell, serous, and mixed endometrial cancer underwent surgery and adjuvant vaginal cuff brachytherapy. Seventy-six patients received chemotherapy. High-dose rate vaginal cuff brachytherapy was planned to a total dose of 21 gray in three fractions using a multichannel vaginal cylinder. The primary objective was to determine the effectiveness of adjuvant vaginal cuff brachytherapy and to identify surgicopathological risk factors that could portend towards worse oncological outcomes.

Results: A total of 182 patients were included in the analysis. Median follow-up was 5.3 years (2.3-12.2). Ten-year survival was 73.3%. Five-year cumulative incidence (CI) of vaginal, pelvic, and para-aortic relapse was 1.4%, 2.1%, and 0.9%, respectively. Five-year locoregional failure, any recurrence, peritoneal relapse, and other distant recurrence was 4.4%, 11.6%, 5.3%, and 6.7%, respectively. On univariate analysis, locoregional failure was worse for larger tumors (per 1 cm) (HR 1.9, 95% CI 1.2 to 3.0, p≤0.01). Any recurrence was worse for tumors of at least 3.5 cm (HR 3.8, 95% CI 1.3 to 11.7, p=0.02) and patients with positive/suspicious cytology (HR 4.4, 95% CI 1.5 to 12.4, p≤0.01). Ten-year survival for tumors of at least 3.5 cm was 56.9% versus 86.6% for those with smaller tumors (HR 2.9, 95% CI 1.4 to 5.8, p≤0.01). Ten-year survival for positive/suspicious cytology was 50.9% versus 77.4% (HR 2.2, 95% CI 0.9 to 5.4, p=0.09). Multivariate modeling demonstrated worse locoregional failure, any recurrence, and survival with larger tumors, as well as any recurrence with positive/suspicious cytology. Subgroup analysis demonstrated improved outcomes with the use of adjuvant chemotherapy in patients with large tumors or positive/suspicious cytology.

Conclusion: Adjuvant vaginal cuff brachytherapy alone without chemotherapy is an appropriate treatment for women with negative peritoneal cytology and small, early-stage clear cell, serous, and mixed endometrial cancer. Larger tumors or positive/suspicious cytology are at increased risk for relapse and worse survival, and should be considered for additional upfront adjuvant treatments, such as platinum-based chemotherapy.
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http://dx.doi.org/10.1136/ijgc-2020-002217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223628PMC
June 2021

Radiation and immunotherapy: emerging mechanisms of synergy.

J Thorac Dis 2020 Nov;12(11):7011-7023

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Immunotherapy (IO) has become a standard treatment in patients with metastatic and locally advanced non-small cell lung cancer (NSCLC), and is now being tested in patients with early stage disease. IO agents currently in use for lung cancer target PD-1, PD-L1, and CTLA-4. While survival and tumor control have improved with IO, many patients have limited or short responses to IO. Therefore, methods to improve the systemic response to IO are needed. Radiation therapy (RT) is an integral component of lung cancer treatment, and may improve systemic response to IO by increasing antigen presentation, increasing co-stimulatory signaling, increasing T-cells recruitment, upregulating PD-L1, increasing tumor stromal lymphocyte infiltration, and altering the microenvironment. IO after definitive chemoradiation is now standard treatment in unresectable stage III NSCLC following publication of the PACIFIC clinical trial. For early stage NSCLC, IO is being investigated in conjunction with stereotactic body radiotherapy (SBRT). The benefit of adding RT to IO in patients with metastatic disease may be especially pronounced in patients with low baseline PD-L1 expression, potentially when delivered as a short course of SBRT, as supported by the PEMBRO-RT clinical trial. Current and ongoing clinical trials are evaluating the optimal radiation dose, timing, and sequencing of RT with IO.
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http://dx.doi.org/10.21037/jtd-2019-cptn-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711365PMC
November 2020

Radiation dermatitis in patients treated with concurrent trastuzumab emtansine (T-DM1).

Clin Transl Radiat Oncol 2020 Sep 3;24:99-101. Epub 2020 Jul 3.

Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.

Trastuzumab Emtansine (T-DM1) improves outcomes for patients with HER2+ breast cancer, and is given concurrently with radiation. We have noted increased radiation dermatitis in these patients, which may have been underreported on the KATHERINE clinical trial, and call for clinicians to remain vigilant of unexpected toxicities with newly approved therapies.
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http://dx.doi.org/10.1016/j.ctro.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369349PMC
September 2020

Patient-Reported Quality of Life Before and After Chemoradiation for Intact Pancreas Cancer: A Prospective Registry Study.

Pract Radiat Oncol 2021 Jan-Feb;11(1):e63-e69. Epub 2020 Jul 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: Our purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer.

Methods And Materials: We reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively.

Results: Of 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL.

Conclusions: For patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.
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http://dx.doi.org/10.1016/j.prro.2020.06.011DOI Listing
July 2020

Assessment of Familiarity With Work-up Guidelines for Bone and Soft Tissue Sarcoma Among Primary Care Practitioners in Minnesota.

Mayo Clin Proc Innov Qual Outcomes 2020 Apr 18;4(2):143-149. Epub 2020 Mar 18.

Mayo Clinic Alix School of Medicine, Rochester, MN.

Objective: To assess familiarity with sarcoma guidelines among primary care practitioners (PCPs) in Minnesota.

Participants And Methods: Surveys were distributed at 2 educational conferences held in Minnesota on April 16-17, 2015, and October 24, 2015. The PCPs were asked a series of questions about their current practice, past experience with sarcoma, and familiarity with sarcoma guidelines. They were then given a series of case presentations and asked to indicate if they would pursue a sarcoma work-up given the information provided.

Results: The study group included 80 physicians and 32 nurse practitioners (NPs). Over their careers (median, 14 years), physicians reported seeing a mean of 2.2 cases of soft tissue sarcoma and 0.7 cases of bone sarcoma. The NPs reported seeing a mean of 0.7 and 0.2 cases, respectfully, over their careers (median, 8 years). Both physicians and NPs reported low familiarity with sarcoma guidelines. When challenged with case presentations for which urgent referral to a sarcoma specialist is recommended, more than 50% of PCPs did not indicate that they would refer patients. The PCPs who had previous experience with soft tissue sarcoma and bone sarcoma estimated that only 17% and 23% of their patients, respectively, were diagnosed within 1 month of presentation. The most reported reason for a delayed diagnosis was the PCP advising the patient to "watch and wait."

Conclusion: Minnesota PCPs have seen very few cases of sarcoma and report low familiarity with sarcoma guidelines. When challenged with case presentations, PCPs made decisions inconsistent with established guidelines. This study supports ongoing efforts to increase sarcoma awareness.
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http://dx.doi.org/10.1016/j.mayocpiqo.2019.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140016PMC
April 2020

Surgery for Mesothelioma After Radiation Therapy (SMART); A Single Institution Experience.

Front Oncol 2020 24;10:392. Epub 2020 Mar 24.

Division of Thoracic Surgery, Mayo Clinic, Rochester, MN, United States.

The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We aimed to assess outcomes and toxicities of treating localized MPM with neoadjuvant radiation therapy (RT) followed by extrapleural pneumonectomy (EPP). Patients were enrolled on an institutional protocol of surgery for mesothelioma after radiation therapy (SMART) between June 2016 and May 2017. Eligible patients were adults with MPM localized to the ipsilateral pleura. Patients underwent staging with PET/CT, pleuroscopy, bronchoscopy/EBUS, mediastinoscopy, and laparoscopy. Five fractions of RT were delivered using intensity modulated radiation therapy (IMRT), with 30 Gy delivered to gross disease and 25 Gy to the entire pleura. EPP was performed 4-10 days following completion of RT. Five patients were treated on protocol. Median age was 62 years (range 36-66). Histology was epithelioid on initial biopsy in all patients, but one was found to have biphasic histology after surgery. Three patients had surgeon-assessed gross total resection, and two had gross residual disease. While all patients were clinically node negative by pretreatment staging, three had positive nodal disease at surgery. Patients were hospitalized for a median 24 days (range 5-69) following surgery. Two patients developed empyema, one of whom developed respiratory failure and subsequently renal failure requiring dialysis, while the other required multiple surgical debridements. Two patients developed atrial fibrillation with rapid ventricular response after surgery, one of whom developed acute respiratory distress requiring intubation and tracheostomy. At last follow-up, one patient died at 1.4 years after local and distant progression, two were alive with local and distant progression, and the remaining two were alive without evidence of disease at 0.1 and 2.7 years. Median time to progression was 9 months. Three patients received salvage chemotherapy. SMART provided promising oncologic outcomes at the cost of significant treatment related morbidity. Due to the significant treatment associated morbidity and favorable treatment alternatives, we have not broadly adopted SMART at our institution.
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http://dx.doi.org/10.3389/fonc.2020.00392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105743PMC
March 2020

Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma.

Neuro Oncol 2020 06;22(6):830-837

Wake Forest Baptist Health, Winston-Salem, North Carolina.

Background: The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma.

Methods: Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection.

Results: For all patients, median overall survival (OS) was 8.4 years (95% CI: 7.2-10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3-6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve 15-year OS (22.4%) versus low-dose radiation (24.9%, log-rank P = 0.978) or 15-year PFS (high dose, 15.2% vs low dose, 9.5%; P = 0.7142). OS was significantly better for patients with preoperative tumor diameter <5 cm and baseline Mini-Mental State Examination (MMSE) >27 and who underwent gross total resection. PFS was improved for patients with oligodendroglioma versus astrocytoma, preoperative tumor diameter <5 cm, patients who had gross total resection, and patients with baseline MMSE >27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years.

Conclusions: Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Cognitive function appeared to be stable after radiation as measured by MMSE.
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http://dx.doi.org/10.1093/neuonc/noaa021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283016PMC
June 2020

A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases.

Neuro Oncol 2019 08;21(8):1049-1059

Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.

Background: Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known.

Methods: Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical ("sugarcoating," cLMD).

Results: The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not.

Conclusions: Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical "sugarcoating" LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.
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http://dx.doi.org/10.1093/neuonc/noz049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682204PMC
August 2019

Predictors of relapse and evaluation of the role of postoperative radiation therapy in a modern series of patients with surgically resected stage III (N2) non-small cell lung cancer.

Adv Radiat Oncol 2017 Jan-Mar;2(1):12-18. Epub 2016 Dec 21.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: For patients with stage III (N2) non-small cell lung cancer (NSCLC) treated with surgical resection, postoperative chemotherapy improves overall survival (OS), but the role of postoperative radiation therapy (PORT) is controversial. The purpose of this study was to evaluate risk factors for local-regional recurrence and to evaluate the impact of PORT on local-regional control (LRC) and OS in a modern series of patients with surgically resected stage III (N2) NSCLC.

Methods And Materials: A retrospective review was performed of patients with Stage III (N2) NSCLC who underwent curative intent resection at our institution between February 1999 and January 2012. OS, LRC, and metastasis-free survival were estimated from the date of surgery using the Kaplan Meier method.

Results: A total of 71 patients were included in the study. Patient median age was 63 years. Histology was adenocarcinoma in 69% of patients. Pretreatment positron emission tomography/computed tomography staging was performed for 90% of patients, and preoperative chemotherapy was administered in 23%. The rate of R0 resection was 96%. Forty-one patients (58%) received PORT and the median PORT dose was 50 Gy (range, 41.4-60 Gy). The median follow-up time for living patients was 5.0 years. Five-year OS for all patients was 66%. OS at 5 years for patients who received PORT compared with patients who did not receive PORT was 71% versus 60%, respectively (hazard ratio [HR], 0.61; 95% CI, 0.30-1.44; = .28). LRC at 5 years for patients who received PORT compared with patients who did not receive PORT was 89% versus 76%, respectively (HR, 0.44; 95% CI, 0.13-1.45; = .17). Factors associated with decreased LRC were male sex ( = .011) and primary tumor (pT) stage (pT3/4 vs. pT1/2, = .006). Metastasis-free survival at 5 years for patients who received PORT compared with those who did not receive PORT was 62% versus 63%, respectively (HR, 1.07; 95% CI, 0.51-2.40; = .86).

Conclusions: In this modern series of patients with resected stage III (N2) NSCLC, patients who received PORT had higher rates of OS and LRC, but these differences were not statistically significant.
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http://dx.doi.org/10.1016/j.adro.2016.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514239PMC
December 2016

Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy.

Pediatr Blood Cancer 2017 Nov 11;64(11). Epub 2017 Jul 11.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs).

Materials And Methods: We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014.

Results: Thirty-four patients received induction chemotherapy followed by radiation with or without surgery. Median follow-up was 11.1 years (0.8-23.3). Outcomes were significantly improved in these 34 patients (5-year overall survival [OS]: 88% versus 50%, P = 0.0092), so analysis is restricted to that subset. Disease-free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid-α-fetoprotein (CSF-AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P = 0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF-AFP at baseline. All three patients with ventricular relapse received local radiation therapy.

Conclusions: NGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF-AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second-look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.
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http://dx.doi.org/10.1002/pbc.26637DOI Listing
November 2017
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