Publications by authors named "Chandana Reddy"

174 Publications

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

JAMA Netw Open 2021 Jul 1;4(7):e2115312. Epub 2021 Jul 1.

Department of Urology, Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland.

Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown.

Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment.

Design, Setting, And Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020.

Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT).

Main Outcomes And Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models.

Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001).

Conclusions And Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.15312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251338PMC
July 2021

Ten-Year Experience in Implementing Single-Fraction Lung SBRT for Medically Inoperable Early-Stage Lung Cancer.

Int J Radiat Oncol Biol Phys 2021 May 26. Epub 2021 May 26.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: To review 10 years of using single-fraction lung stereotactic body radiation therapy (SF-SBRT) for medically inoperable peripheral early-stage lung cancer.

Methods And Materials: An institutional review board-approved prospective lung SBRT data registry was surveyed until the end of December 2019 for all patients receiving SF-SBRT with minimum 6-month follow-up. Doses used were either 34 Gy or 30 Gy. Outcomes of interest included rates of local failure and overall survival (OS), as well as treatment-related toxicity graded per Common Terminology Criteria for Adverse Events version 3.0.

Results: A total of 229 patients met the study criteria. Patient characteristics included female sex (55%); median age, 74.6 years (range, 47-94); and median Karnofsky Performance Status 80 (range, 50-100). Tumor characteristics included median diameter, 1.6 cm (range, 0.7-4.1); median positron emission tomography standardized uptake value maximum 6.1 (range, 0.8-24.3); and 63.6% of patients biopsied. SF-SBRT dose was 34 Gy in 72.1% cases and 30 Gy in 27.9%, with patient and tumor characteristics balanced between cohorts. Overall median follow-up times for 30 Gy and 34 Gy were 36.7 and 17.2 months, respectively (P < .0001). At analysis, 55.9% patients were alive. Two (0.9%) patients developed grade 3 toxicities, and none had grade 4/5 toxicities. Grades 1 to 2 pneumonitis and chest wall toxicity were seen in 7% and 12.7% patients, respectively. Median overall survival was 44.1 months. Rates of 2-year local, nodal, and distant failure were 7.3%, 9.4%, and 12.2%, respectively. There were no significant differences in outcomes by dose.

Conclusions: This is the largest institutional series to date reporting on SF-SBRT outcomes for medically inoperable peripheral early-stage lung cancer and the first to report on a decade's experience in implementing this schedule. Outcomes from this analysis are comparable to published results from 2 randomized trials and validate the use of this schedule in routine practice. In the absence of phase 3 trials, this study should encourage increased use of SF-SBRT for inoperable tumors.
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http://dx.doi.org/10.1016/j.ijrobp.2021.05.116DOI Listing
May 2021

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

Eur Urol 2021 Aug 10;80(2):142-146. Epub 2021 May 10.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.04.035DOI Listing
August 2021

Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience.

J Radiosurg SBRT 2021 ;7(3):189-197

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Purpose/objectives: Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) in the setting of oligometastatic disease is a rapidly evolving paradigm given ongoing improvements in systemic therapies and diagnostic modalities. However, SBRT to targets in the abdomen and pelvis is historically associated with concerns about toxicity. The purpose of this study was to evaluate the safety and efficacy of SBRT to the abdomen and pelvis for women with oligometastases from primary gynecological tumors.

Materials/methods: From our IRB-approved registry, all patients who were treated with SBRT between 2014 and 2020 were identified. Oligometastatic disease was defined as 1 to 5 discrete foci of clinical metastasis radiographically diagnosed by positron emission tomography (PET) and/or computerized tomography (CT) imaging. The primary endpoint was local control at 12 months. Local and distant control rates were estimated using the Kaplan-Meier method. Time intervals for development of local progression and distant progression were calculated based on follow up visits with re-staging imaging. Acute and late toxicity outcomes were determined based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Results: We identified 34 women with 43 treated lesions. Median age was 68 years (range 32-82), and median follow up time was 12 months (range 0.2-54.0). Most common primary tumor sites were ovarian (n=12), uterine (n=11), and cervical (n=7). Median number of previous lines of systemic therapy agents at time of SBRT was 2 (range 0-10). Overall, SBRT was delivered to 1 focus of oligometastasis in 29 cases, 2 foci in 2 cases, 3 foci in 2 cases, and 4 foci in 1 case. All patients were treated comprehensively with SBRT to all sites of oligometastasis. Median prescription dose was 24 Gy (range 18-54 Gy) in 3 fractions (range 3-6) to a median prescription isodose line of 83.5% (range 52-95). Local control by lesion at 12 and 24 months was 92.5% for both time points. Local failure was observed in three treated sites among two patients, two of which were at 11 months in one patient, and the other at 30 months. Systemic control rate was 60.2% at 12 months. Overall survival at 12 and 24 months was 85% and 70.2%, respectively. Acute grade 2 toxicities included nausea (n=3), and there were no grade > 3 acute toxicities. Late grade 1 toxicities included diarrhea (n=1) and fatigue (n=1), and there were no grade > 2 toxicities.

Conclusion: SBRT to oligometastatic gynecologic malignancies in the abdomen and pelvis is feasible with encouraging preliminary safety and local control outcomes. This approach is associated with excellent local control and low rates of toxicity during our follow-up interval. Further investigations into technique, dose-escalation and utilization are warranted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055243PMC
January 2021

Risk Assessment in Thyroid Lobectomy and Total Thyroidectomy using Over 100 Thousand Cases.

Ann Otol Rhinol Laryngol 2021 Apr 9:34894211007219. Epub 2021 Apr 9.

Head and Neck Institute, The Cleveland Clinic, Cleveland, OH, USA.

Objectives: To assess risk factors and non-thyroid specific postoperative complications for thyroid lobectomy compared to total thyroidectomy.

Methods: A retrospective, cross-sectional study of adults undergoing a lobectomy or total thyroidectomy using the National Surgical Quality Improvement Program database between 2005 and 2017. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded.

Results: A total of 106 915 patients were analyzed, 64 763 total thyroidectomies and 42 152 lobectomies. Multivariable analysis demonstrated that total thyroidectomy patients were half as likely to return to the operating room (OR = 0.491 (95%CI 0.445-0.542),  < .001). Within this cohort, patients at greater risk for reoperation had a history of hypertension (OR = 1.225 (95%CI 1.090-1.376),  < .001), a malignant pathology (OR = 1.921 (95%CI 1.734-2.128),  < .001), and smoked (OR = 1.237 (95%CI 1.087-1.407),  = .001). Conversely, diabetes and body mass index did not impact the rate of reoperation when assessing total thyroidectomy and lobectomy. The most frequent non-thyroid specific complications in total thyroidectomy were unplanned intubation (0.5%), urinary tract infection (0.3%), and superficial surgical site infection (0.3%). In thyroid lobectomy, the most common complications were superficial surgical site infection (0.3%) and urinary tract infection (0.2%).

Conclusions: Our multi-institutional study indicates specific risk factors for returning to the operating room that may warrant closer follow up after surgery for total thyroidectomy or thyroid lobectomy. We also identified the most common post-operative complications. During pre-operative planning, these findings should be considered by thyroid surgeons to help mitigate risk to patients.
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http://dx.doi.org/10.1177/00034894211007219DOI Listing
April 2021

Oncologic outcomes among Black and White men with grade group 4 or 5 (Gleason score 8-10) prostate cancer treated primarily by radical prostatectomy.

Cancer 2021 May 15;127(9):1425-1431. Epub 2021 Mar 15.

Department of Urology, University of Washington, Seattle, Washington.

Background: The aim of this study was to describe pathologic and short-term oncologic outcomes among Black and White men with grade group 4 or 5 prostate cancer managed primarily by radical prostatectomy.

Methods: This was a multi-institutional, observational study (2005-2015) evaluating radical prostatectomy outcomes by self-identified race. Descriptive analysis was performed via nonparametric statistical testing to compare baseline clinicopathologic data. Univariable and multivariable time-to-event analyses were performed to assess biochemical recurrence (BCR), metastasis, cancer-specific mortality (CSM), and overall survival between Black and White men.

Results: In total, 1662 men were identified with grade group 4 or 5 prostate cancer initially managed by radical prostatectomy. Black men represented 11.3% of the cohort (n = 188). Black men were younger, demonstrated a longer time from diagnosis to surgery, and were at a lower clinical stage (all P < .05). Black men had lower rates of pT3/4 disease (49.5% vs 63.5%; P < .05) but higher rates of positive surgical margins (31.6% vs 26.5%; P = .14) on pathologic evaluation. There was no difference in BCR, CSM, or overall survival over a median follow-up of 40.7 months. Black men had a lower 5-year cumulative incidence of metastasis-free survival (93.6%; 95% confidence interval [CI], 86.5%-97.0%) in comparison with White men (85.8%; 95% CI, 83.1%-88.0%), which did not persist in an age-adjusted analysis.

Conclusions: Black and White men with high-grade prostate cancer at diagnosis demonstrated similar oncologic outcomes when they were managed by primary radical prostatectomy. Our findings suggest that racial disparities in prostate cancer mortality are not related to differences in the efficacy of extirpative therapy.
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http://dx.doi.org/10.1002/cncr.33419DOI Listing
May 2021

Failure rate in the untreated contralateral node negative neck of small lateralized oral cavity cancers: A multi-institutional collaborative study.

Oral Oncol 2021 04 11;115:105190. Epub 2021 Feb 11.

Department of Cancer Services, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Queensland, Australia; Faculty of Medicine, University of Queensland, St. Lucia, Australia.

Objectives: The importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment.

Materials And Methods: We performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS).

Results: 176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2-7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4-32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2-95.0%) and 80.6% (95% CI 74.5-86.8%), respectively.

Conclusion: Observation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105190DOI Listing
April 2021

Risk of thromboembolism in patients with ALK- and EGFR-mutant lung cancer: A cohort study.

J Thromb Haemost 2021 03 24;19(3):822-829. Epub 2021 Jan 24.

Department of Hematology & Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Introduction: Thromboembolism (TE) is common in patients with non-small cell lung cancer (NSCLC) and is associated with worse outcomes. Recent advances in the understanding of NSCLC have led to the identification of molecular subtypes such as anaplastic lymphocyte kinase (ALK) and epidermal growth factor receptor (EGFR) mutations. The association of these subtypes with risk of TE has not been fully explored.

Methods: We conducted a retrospective cohort study of consecutive NSCLC patients seen at the Cleveland Clinic from July 2002 through July 2017 for whom molecular classification and follow-up were available. TE events included deep vein thrombosis (DVT), pulmonary embolism (PE), visceral vein thrombosis (VVT), and arterial events. TE-free survival and overall survival rates for each of the molecular subtypes (wild-type, ALK-mutant, and EGFR-mutant) were estimated by the Kaplan-Meier method. Cox proportional hazard regression analysis was used to identify factors associated with the endpoints TE and overall survival. TE was analyzed as a conditional, time-dependent covariate to assess its impact with respect to overall survival.

Results: The study population consisted of 461 patients. Approximately half were females (n = 263, 57%) and 58% (n = 270) were older than 65 years. TE occurred in 98 of 461 patients (21.3%) during a median follow-up of 33.1 months. The highest cumulative rates of TE were observed in patients with ALK-mutant NSCLC (N = 20/46, 43.5%) followed by patients with EGFR-mutant cancers (N = 35/165, 21.2%) and wild-type cancers (N = 43/250, 17.2%) P < .05. Cumulative incidence of TE at 6 months of follow-up was 15.7% (95% confidence interval [CI]: 5.0%-26.4%) for ALK-mutant cancers, 8.8% (95% CI: 4.4%-13.2%) for EGFR-mutant cancers, and 9.2% (95% CI: 5.4%-12.9%) for wild-type cancers. Patients who experienced TE had worse overall survival (all patients: hazard ratio = 2.8 95% CI 2.1-3.6, P < .001).

Conclusions: Patients with ALK-mutant advanced lung adenocarcinoma have the highest rate of TE. TE is associated with worse survival across molecular subtypes. These findings should be taken into consideration in decision-making regarding thromboprophylaxis.
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http://dx.doi.org/10.1111/jth.15215DOI Listing
March 2021

Organizing pneumonia secondary to infection in a kidney transplant recipient: Case report and review of literature.

Lung India 2020 Sep-Oct;37(5):441-444

Department of Pathology, Star Hospitals, Hyderabad, Telangana, India.

Organizing pneumonia (OP), previously known as bronchiolitis obliterans OP, is a diffuse parenchymal lung disease affecting the distal bronchioles, alveolar ducts, and alveolar walls. Pulmonary infections, especially bacterial and viral diseases, are known to be associated with the secondary form of OP. OP secondary to fungal infections is less common. Here, we report a case of OP associated with pneumocystis pneumonia (PCP) in a kidney transplant recipient on tacrolimus-based triple immunosuppression. The index case had developed new lung consolidation toward the end of trimethoprim-sulfamethoxazole therapy for PCP. Spontaneous clinical and radiographic resolution was seen without any increment in the dose of corticosteroids. We review the literature and present a summary of all reported cases of OP associated with PCP to date.
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http://dx.doi.org/10.4103/lungindia.lungindia_487_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857385PMC
September 2020

A National Comparison of Postoperative Outcomes in Completion Thyroidectomy and Total Thyroidectomy.

Otolaryngol Head Neck Surg 2021 03 25;164(3):566-573. Epub 2020 Aug 25.

Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Objective: To characterize and assess the non-thyroid-specific postoperative complications of completion thyroidectomy as compared with total thyroidectomy.

Study Design: Retrospective analysis: 2005 to 2017.

Setting: National Surgical Quality Improvement Program database.

Subjects And Methods: Patients aged >18 years receiving a completion or total thyroidectomy were eligible for inclusion. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded.

Results: A total of 70,638 patients were analyzed, representing 64,763 total thyroidectomies and 5875 completion thyroidectomies. The 30-day mortality rate was 0.1% for both procedures ( > .05). Overall, 1.7% and 1.4% of patients undergoing total and completion thyroidectomies experienced at least 1 complication ( > .05), while 1.2% and 0.9% had a postoperative medical complication ( = .0186), respectively. On multivariable analysis, patients undergoing total thyroidectomies were significantly more likely to return to the operating room (odds ratio [OR], 1.36; 95% CI, 1.04-1.80; = .027) and to be readmitted (OR, 1.45; 95% CI, 1.16-1.81; = .001). Adjusted analysis also demonstrated that patients undergoing total thyroidectomies were more likely to be inpatients (OR, 1.17; 95% CI, 1.11-1.24; < .001), be treated by nonotolaryngologists (OR, 1.36; 95% CI, 1.29-1.45; < .001), and smoke (OR, 1.22; 95% CI, 1.13-1.33; < .001).

Conclusion: National data suggest that total and completion thyroidectomies are relatively safe procedures but that completion thyroidectomies are associated with lower rates of postoperative complications. These findings may play a role in determining treatment plans for patients and optimizing risk reduction.
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http://dx.doi.org/10.1177/0194599820951165DOI Listing
March 2021

Pulmonary tuberculosis presenting as diffuse cystic lung disease: An atypical manifestation.

Indian J Tuberc 2020 Jul 27;67(3):397-399. Epub 2019 Nov 27.

Department of Pulmonary and Critical Care Medicine, Star Hospitals, Hyderabad, India.

Pulmonary tuberculosis has varied patterns of clinical presentation. Here, we report a case of tuberculosis in a 44 year immunocompetent female patient who presented to us with multiple cysts in the lung parenchyma. The diagnosis was confirmed by the analysis of bronchoalveolar lavage fluid. She had secondary spontaneous pneumothorax and progressive respiratory failure despite anti-tubercular therapy. Acute or sub acute onset of multiple lung cysts is usually associated with pulmonary infection. Tuberculosis presenting as cystic lung disease is less common and atypical. High index of suspicion and early initiation of therapy is pivotal in management of such cases.
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http://dx.doi.org/10.1016/j.ijtb.2019.11.016DOI Listing
July 2020

Clinical Versus Pathologic Laryngeal Cancer Staging and the Impact of Stage Change on Outcomes.

Laryngoscope 2021 03 21;131(3):559-565. Epub 2020 Jul 21.

Department of Otolaryngology-Head and Neck Surgery, University of Missouri, Columbia, Missouri, U.S.A.

Objectives/hypothesis: Evaluate the impact and accuracy of clinical laryngeal cancer staging.

Study Design: Retrospective cohort study.

Methods: Two hundred sixty-five consecutive patients with laryngeal squamous cell carcinoma who underwent total laryngectomy from 2001 to 2017 were studied. Clinical versus pathologic tumor (T) and nodal (N) categories were compared. Logistic regression and Cox proportional hazards analyzed the association of stage change with perioperative factors and outcomes.

Results: Forty-seven patients (17.7%, accuracy = 0.969 ± 0.010 [standard error]) changed between T1-2 and T3-4. Sixty-four patients (24.1%, accuracy = 0.866 ± 0.020) had inaccurate N category. Salvage patients were less likely to have stage change (downstage: odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.08-0.50, P < .001; upstage: OR = 0.41, 95% CI: 0.23-0.74, P = .003), but more likely to have inaccurate nodal category (39.8% vs. 11.7%, P < .001). Patients with stage change tended to have greater odds of positive/close margins (upstage: OR = 1.78, 95% CI: 0.91-3.5, P = .092) and chemotherapy (downstage: OR = 2.21, 95% CI: 0.80-6.14, P = .128; upstage: OR = 1.87, 95% CI: 0.85-4.11, P = .119). Stage change was associated with recurrence (P = .047) with downstaged patients less likely to recur (hazard ratio = 0.26, 95% CI: 0.08-0.82, P = .021). Stage change was not associated with positron emission tomography scan, subsite, time to surgery, or mortality.

Conclusions: A third of laryngeal cancer patients were downstaged or upstaged after laryngectomy with 18% and 24% of clinical T and N categories inaccurate, respectively. Stage change was less common for salvage patients and associated with risk of recurrence.

Level Of Evidence: 3 Laryngoscope, 131:559-565, 2021.
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http://dx.doi.org/10.1002/lary.28924DOI Listing
March 2021

Salvage Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Primary Surgical Resection of Non-small-cell Lung Cancer.

Clin Lung Cancer 2021 May 2;22(3):e360-e365. Epub 2020 Jun 2.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Introduction: We sought to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) as salvage treatment for local recurrence after prior surgical resection for non-small-cell lung cancer (NSCLC).

Materials And Methods: We surveyed our prospective lung SBRT registry for patients who received salvage SBRT (sSBRT) for local recurrence after previous resection of a primary NSCLC. Following sSBRT, local control, distant metastases, overall survival, and treatment-related toxicity were evaluated.

Results: From 2004 to 2017, 48 patients met inclusion criteria. At initial surgery, 44 (83%) patients had stage I to II disease, and surgical approaches were 47.9% wedge resection, 4.2% segmentectomy, 43.8% lobectomy, and 4.2% bilobectomy. The median time to local recurrence after surgery was 26.4 months, and 36 (75%) recurrences were biopsy-proven. Surgical salvage was not possible owing to un-resectability or underlying comorbidities in 45 (93.8%) patients. Most (68.8%) patients received 50 Gy in 5 fractions. The median follow-up after sSBRT was 22.6 months (range, 3.8-108.8 months). Eight (16.7%) patients experienced local or lobar failure, and 9 (19.1%) patients had nodal failure at a median of 12.5 months (range, 2-66.1 months). Nineteen (39.6%) patients failed distantly at a median of 11.4 months. The median overall survival after sSBRT was 29.3 months. A total of 72.9% of patients experienced no toxicity after sSBRT. Three (6.3%) patients developed grade III toxicity (cough, atelectasis, or soft tissue necrosis) following sSBRT.

Conclusions: Similar to SBRT for primary early stage NSCLC, sSBRT for local relapse following surgical resection of NSCLC offers high rates of local control with limited toxicity. Distant failure remains the primary pattern of failure.
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http://dx.doi.org/10.1016/j.cllc.2020.05.025DOI Listing
May 2021

Outpatient Anesthesia Facilitates Stereotactic Body Radiation Therapy for Early Stage Lung Cancer Patients With Advanced Cognitive Impairments.

Adv Radiat Oncol 2020 May-Jun;5(3):444-449. Epub 2019 Oct 14.

Department of Radiation Oncology, Taussig Cancer Centre, Cleveland Clinic, Cleveland, Ohio.

Purpose: To report on the use of outpatient anesthesia (OPA) facilitating delivery of stereotactic body radiation therapy (SBRT) in patients with severe cognitive impairments (CI) diagnosed with inoperable early stage lung cancer.

Methods And Materials: We surveyed our institutional review board-approved prospective lung SBRT data registry to document the feasibility of using anesthesia in CI patients and to determine their SBRT outcomes.

Results: From 2004 to 2018, 8 from a total 2084 patients were identified for this analysis. The median age at treatment was 68 years (range, 44-78). Most patients were female (62.5%). CI diagnoses included Alzheimer-related dementia (3 patients), chronic schizophrenia (3 patients), severe anxiety disorder (1 patient), and severe developmental disability (1 patient). The median tumor size was 3.4 cm (range, 1.1-10.5), and 7 patients (87.5 %) had central lesions. The median follow-up time was 22.5 months. The most common (50%) SBRT schedule used was 50 Gy in 5 fractions. Intravenous propofol (10 mg/mL) was used for OPA in all cases at the time of simulation and with daily treatments. OPA was well tolerated and all patients completed SBRT as prescribed. There was one grade 5 but no other grade 3 or higher SBRT-related toxicities. One patient died with local failure and one of distant failure.

Conclusions: OPA made lung SBRT feasible for patients with CIs. SBRT outcomes were in keeping with those reported in the literature. CI should not be considered a contraindication per se to SBRT delivery in patients otherwise appropriate for this modality.
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http://dx.doi.org/10.1016/j.adro.2019.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276662PMC
October 2019

Gantry-Mounted Linear Accelerator-Based Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer.

Adv Radiat Oncol 2020 May-Jun;5(3):404-411. Epub 2019 Oct 14.

Department of Radiation Oncology, University of California, Los Angeles, California.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer.

Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity.

Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity ( < .001) and weekly fractionation ( < .01), although only 12.4% of patients were treated weekly.

Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.
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http://dx.doi.org/10.1016/j.adro.2019.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276661PMC
October 2019

Does neck dissection affect post-operative outcomes in parotidectomy? A national study.

Am J Otolaryngol 2020 Sep - Oct;41(5):102593. Epub 2020 Jun 5.

Head and Neck Institute, The Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Objective: To characterize post-operative complications in parotidectomy with neck dissection.

Methods: Patients age ≥ 18 receiving a parotidectomy or parotidectomy with neck dissection between 2005 and 2017 were eligible for inclusion. Patients with unknown demographic variables were excluded. Univariate and multivariable logistic regression analyses were performed.

Results: A total of 13,609 parotidectomy patients were analyzed, 11,243 (82.6%) without neck dissection and 2366 (17.4%) with neck dissection. Both length of surgery (mean minutes ± standard deviation [SD] = 335.9 ± 189.2 vs. 152.9 ± 99.0, p < 0.001) and length of hospital stay (mean days ± SD = 3.90 ± 4.76 vs. 1.04 ± 2.14, p < 0.001) were greater with dissection. 13.9% of parotidectomies with neck dissection and 3.5% without dissection (p < 0.001) had at least one complication, which remained significant after multivariable adjustment (Odds Ratio[OR] = 1.565 (95%CI = 1.279-1.914), p < 0.001). The increase in post-operative complications was predominately driven by an increased transfusion rate (7.4% vs. 0.5%, p < 0.001). Multivariable analysis also demonstrated no significant difference in rates of returning to the operating room (OR = 1.122 (95%CI 0.843-1.493), p > 0.05) or rates of readmission (OR = 1.007 (95%CI 0.740-1.369), p > 0.05). Parotidectomy with neck dissection was more likely to be inpatient (OR = 4.411 (95%CI 3.887-5.004), p < 0.001) and to be ASA class 3 (OR = 1.367 (95%CI 1.194-1.564), p < 0.001).

Conclusions: Nationwide data demonstrates that parotidectomy with neck dissection is associated with increased rates of post-operative complications; however, neck dissection did not significantly impact readmission or reoperation rates. These findings indicate that neck dissection is a relatively safe addition to parotidectomy and provide novel evidence in the management of parotid malignancies.
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http://dx.doi.org/10.1016/j.amjoto.2020.102593DOI Listing
November 2020

Analyzing the role of adjuvant or salvage radiotherapy for spinal myxopapillary ependymomas.

J Neurosurg Spine 2020 May 1:1-6. Epub 2020 May 1.

3Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic; and Departments of.

Objective: The authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE).

Methods: The authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized.

Results: Of the 59 patients included in the study, the median age at initial surgery was 34 years (range 12-74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 (25%), and unknown in 5 patients (9%). After surgery, 10 patients (17%) underwent adjuvant RT (5/39 GTR [13%] and 5/15 STR [33%] patients). Median follow-up was 6.2 years (range 0.1-35.3 years). Overall, 20 patients (34%) experienced recurrence (local, n = 15; distant, n = 5). The median RFS was 11.2 years (95% CI 77 to not reached), and the 5- and 10-year RFS rates were 72.3% (95% CI 59.4-86.3) and 54.0% (95% CI, 36.4-71.6), respectively.STR was associated with a higher risk of recurrence (HR 6.45, 95% CI 2.15-19.23, p < 0.001) than GTR, and the median RFS after GTR was 17.2 years versus 5.5 years after STR. Adjuvant RT was not associated with improved RFS, regardless of whether it was delivered after GTR or STR. Of the 20 patients with recurrence, 12 (60%) underwent salvage treatment with surgery alone (GTR, n = 6), 4 (20%) with RT alone, and 4 (20%) with surgery and RT. Compared to salvage surgery alone, salvage RT, with or without surgery, was associated with a significantly longer postrecurrence RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006).

Conclusions: At initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.
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http://dx.doi.org/10.3171/2020.2.SPINE191534DOI Listing
May 2020

Heterogenous Dose-escalated Prostate Stereotactic Body Radiation Therapy for All Risk Prostate Cancer: Quality of Life and Clinical Outcomes of an Institutional Pilot Study.

Am J Clin Oncol 2020 07;43(7):469-476

Department of Radiation Oncology, Taussig Cancer Institute.

Objectives: Previous prostate stereotactic body radiation therapy studies delivered uniform doses of 35 to 40 Gy/5 fx. Attempts at uniform dose escalation to 50 Gy caused high rates of gastrointestinal (GI) toxicity. We hypothesize that heterogeneous dose escalation to regions nonadjacent to sensitive structures (urethra, rectum, and bladder) is safe and efficacious.

Materials And Methods: Patients were enrolled on a prospective pilot study. The primary endpoint was treatment-related GI and genitourinary (GU) toxicity. The secondary endpoints included quality of life (QOL) assessed by the EPIC-26 questionnaire and biochemical control. The target volume received 36.25 Gy/5 fx. The target >3 mm from sensitive was dose escalated to 50 Gy/5 fx.

Results: Thirty-five patients were enrolled. Three patients had low, 14 intermediate, and 18 high-risk disease. The mean initial prostate specific antigen was 15.1 ng/mL. Androgen deprivation therapy was given to 19 patients. Median follow-up was 46 months. Urinary irritation/obstructive and urinary bother scores declined by minimal clinically important difference threshold from baseline at 6 weeks, but subsequently recovered by 4 months. No differences in QOL scores were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 4 GU toxicity and acute grade 4 GI toxicity. The incidence of late high grade toxicity was 1/35 for GU toxicity and 2/35 for GI toxicity. Freedom from biochemical failure at 3 years was 88.0%.

Conclusions: Heterogeneous dose-escalated prostate stereotactic body radiation therapy is feasible with low rates of acute and late toxicities and favorable QOL outcomes in patients with predominantly intermediate-risk and high-risk prostate cancer.
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http://dx.doi.org/10.1097/COC.0000000000000693DOI Listing
July 2020

Recurrence and Progression of Head and Neck Paragangliomas after Treatment.

Otolaryngol Head Neck Surg 2020 Apr 18;162(4):504-511. Epub 2020 Feb 18.

Head & Neck Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Objective: To characterize the recurrence of head and neck paragangliomas and the factors associated with disease progression after treatment.

Study Design: Retrospective cohort study.

Setting: Tertiary care center.

Subjects And Methods: In total, 173 adults with 189 paragangliomas (41.3% carotid body, 29.1% glomus jugulare, 19.0% glomus tympanicum, and 10.6% glomus vagale) treated between 1990 and 2010 were evaluated to determine the incidence and risk of recurrence using Cox proportional hazards.

Results: The mean (SD) follow-up duration was 8.6 (9.1) years. The incidence was 2.92 recurrences per 100 person-years. The rate of recurrence was 8.2% (95% confidence interval [CI], 3.7-12.7) after 4 years and 17.1% (95% CI, 10.2-24.0) after 10 years. Glomus jugulare tumors were more likely to recur (hazard ratio [HR], 3.69; 95% CI, 1.70-8.01; < .001) while carotid body tumors were less likely (HR, 0.44; 95% CI, 0.21-0.97; = .041). Radiation had a lower risk of recurrence or progression compared to surgical excision (HR, 0.30; 95% CI, 0.10-.94; = .040). Recurrence was associated with right-sided paragangliomas (HR, 3.60; 95% CI, 1.63-7.75; = .001). The median time to recurrence was 18.4 years. Six (3.2%) patients developed metastasis, which was more common with local recurrence (9.5% vs 1.4%, = .015).

Conclusions: Recurrence is more common with glomus jugulare tumors and less common with carotid body tumors. Radiation may have a lower risk of recurrence or progression than surgery for some paraganglioma types. Metastasis is rare but more likely with recurrent disease. Surveillance neck imaging is recommended every several years for decades after treatment.
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http://dx.doi.org/10.1177/0194599820902702DOI Listing
April 2020

HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer.

JAMA Oncol 2020 04 9;6(4):e196496. Epub 2020 Apr 9.

GU Malignancies Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Importance: The adrenal-restrictive HSD3B1(1245A) allele limits extragonadal dihydrotestosterone synthesis, whereas the adrenal-permissive HSD3B1(1245C) allele augments extragonadal dihydrotestosterone synthesis. Retrospective studies have suggested an association between the adrenal-permissive allele, the frequency of which is highest in white men, and early development of castration-resistant prostate cancer (CRPC).

Objective: To examine the association between the adrenal-permissive HSD3B1(1245C) allele and early development of CRPC using prospective data.

Design, Setting, And Participants: The E3805 Chemohormonal Therapy vs Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) was a large, multicenter, phase 3 trial of castration with or without docetaxel treatment in men with newly diagnosed metastatic prostate cancer. From July 28, 2006, through December 31, 2012, 790 patients underwent randomization, of whom 527 had available DNA samples. In this study, the HSD3B1 germline genotype was retrospectively determined in 475 white men treated in E3805 CHAARTED, and clinical outcomes were analyzed by genotype. Data analysis was performed from July 28, 2006, to October 17, 2018.

Interventions: Men were randomized to castration plus docetaxel, 75 mg/m2, every 3 weeks for 6 cycles or castration alone.

Main Outcomes And Measures: Two-year freedom from CRPC and 5-year overall survival, with results stratified by disease volume. Patients were combined across study arms according to genotype to assess the overall outcome associated with genotype. Secondary analyses by treatment arm evaluated whether the docetaxel outcome varied with genotype.

Results: Of 475 white men with DNA samples, 270 patients (56.8%) inherited the adrenal-permissive genotype (≥1 HSD3B1[1245C] allele). Mean (SD) age was 63 (8.7) years. Freedom from CRPC at 2 years was diminished in men with low-volume disease with the adrenal-permissive vs adrenal-restrictive genotype: 51.0% (95% CI, 40.9%-61.2%) vs 70.5% (95% CI, 60.0%-80.9%) (P = .01). Overall survival at 5 years was also worse in men with low-volume disease with the adrenal-permissive genotype: 57.5% (95% CI, 47.4%-67.7%) vs 70.8% (95% CI, 60.3%-81.3%) (P = .03). Hazard ratios were 1.89 (95% CI, 1.13-3.14; P = .02) for CRPC and 1.74 (95% CI, 1.01-3.00; P = .045) for death. There was no association between genotype and outcomes in men with high-volume disease. There was no interaction between genotype and benefit from docetaxel.

Conclusions And Relevance: Inheritance of the adrenal-permissive HSD3B1 genotype is associated with earlier castration resistance and shorter overall survival in men with low-volume metastatic prostate cancer and may help identify men more likely to benefit from escalated androgen receptor axis inhibition beyond gonadal testosterone suppression.
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http://dx.doi.org/10.1001/jamaoncol.2019.6496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042830PMC
April 2020

Impact of routine surveillance imaging on detecting recurrence in human papillomavirus associated oropharyngeal cancer.

Oral Oncol 2020 04 7;103:104585. Epub 2020 Feb 7.

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, United States.

Objectives: This study examines the utility of surveillance imaging in detecting locoregional failures (LRF), distant failures (DF) and second primary tumors (SPT) in patients with human papillomavirus (HPV) associated oropharyngeal cancer (OPC) after definitive chemoradiotherapy (CRT).

Methods And Materials: An institutional database identified 225 patients with biopsy proven, non- metastatic HPV+ OPC treated with definitive CRT between 2004 and 2015, whose initial post-treatment imaging was negative for disease recurrence (DR). Two groups were defined: patients with <2 scans/year Group 1 and patients with ≥2 scans/year Group 2. The Mann-Whitney test or Chi-square was used to determine differences in baseline characteristics between groups. Fine & Gray regression was used to detect an association between imaging frequency, DR and diagnosis of SPT.

Results: Median follow up was 40.8 months. 30% of patients had ≥T3 disease and 90% had ≥ N2 disease (AJCC 7th edition). Twenty one failures (9.3%) were observed, 7 LRF and 15 DF. Six LRF occurred within 24 months and 14 DF occurred within 36 months of treatment completion. Regression analysis showed Group 2 had increased risk of DR compared to Group1 (HR 10.3; p = 0.002) albeit with more advanced disease at baseline. Five SPT were found (2 lung, 2 esophagus, and 1 oropharynx) between 4.5 and 159 months post-CRT.

Conclusion: Surveillance imaging seems most useful in the first 2-3 years post treatment, and is particularly important in detecting DF. Surveillance scans for SPT has a low yield, but should be considered for those meeting lung cancer screening guidelines.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104585DOI Listing
April 2020

Investigation of brachial plexus dose that exceeds RTOG constraints for apical lung tumors treated with four- or five-fraction stereotactic body radiation therapy.

J Radiosurg SBRT 2019 ;6(3):189-197

Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, 10201 Carnegie Avenue, Cleveland, OH 44195, USA.

Purpose/objectivess: We sought to determine the rate of brachial plexopathy (BPX) in patients exceeding RTOG dose constraints for treatment of apical lung tumors.

Materials/methods: Patients with apical lung tumors treated with four- or five-fraction SBRT were identified from a prospective registry. Dosimetric data were obtained for ipsilateral subclavian vein (SCV) and anatomic BP (ABP) contours. Cumulative equivalent dose in 2 Gy equivalents (EQD2) was calculated for the SCV contour in patients with a history of prior ipsilateral RT. Five-fraction SBRT RTOG constraints of D0.03cc ≤32.0 Gy and D3cc ≤30.0 Gy were used. BPX was graded according to Common Terminology Criteria for Adverse Events 3.0.

Results: A total of 64 patients met inclusion criteria. Median follow-up was 21 months. Six patients (9.4%) had prior ipsilateral conventional fractionated RT with varying degrees of overlap with subsequent SBRT field. Eleven patients without prior ipsilateral RT exceeded D0.03cc ≤32.0 Gy to SCV (mean 43.8 Gy ± 5.8). No BPX was observed in these patients. Out of the six patients who had prior ipsilateral RT, three patients exceeded D0.03cc ≤32.0 Gy to SCV (44.2 Gy ± 11.3), with two of these patients developing Grade 2 BPX within one year of SBRT. The EQD2 cumulative maximum point dose to BP was 122.6 Gy and 184.7 Gy for the two patients who developed Grade 2 BPX. The D0.03cc was >10 Gy higher to the ABP contour than the SCV contour in 14 patients.

Conclusion: Without a history of prior ipsilateral RT, no BPX was observed at 21 month follow-up in 11 patients who exceeded the RTOG five-fraction BP constraint. This observation is hypothesis generating and more experience with longer follow-up is necessary to validate these findings. For tumors located in close proximity to apical structures, there was substantial variation in dose between the ABP and SCV contours.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774482PMC
January 2019

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy.

Brachytherapy 2020 Jan - Feb;19(1):43-50. Epub 2019 Dec 5.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address:

Purpose: To validate the 2019 NCCN subgroups of favorable- and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification.

Methods: We included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis.

Results: Of 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3-214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00-4.10; p < 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78-5.50, p < 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6-6.1%) vs. 17.0% (95% CI, 13.6-20.5%; p < 0.001), and for distant metastasis were 1.6% (95% CI, 0.5-2.6%) vs. 5.4% (95% CI, 3.3-7.4%; p < 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54-3.36; p < 0.001) and 2-3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89-6.76; p < 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34-4.53, p = 0.004; 2-3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49-9.10, p < 0.001).

Conclusions: These findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted.
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http://dx.doi.org/10.1016/j.brachy.2019.10.005DOI Listing
September 2020

Impact of active smoking on outcomes in HPV+ oropharyngeal cancer.

Head Neck 2020 02 26;42(2):269-280. Epub 2019 Nov 26.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.

Background: The role of smoking among patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is unclear.

Methods: A retrospective cohort study of patients with HPV(+) OPSCC from 2001 to 2015 at a tertiary-care institution was conducted. The primary outcome was overall survival (OS).

Results: Among 484 included patients, 94 (19.4%) were active smokers, 226 (46.7%) were former smokers, and 164 (33.9%) never smoked. Among active smokers, 82 patients (87.2%) had a ≥10 pack-year and 69 (73.4%) had a ≥20 pack-year smoking history. After adjusting for covariates, active smoking was a significant predictor of inferior OS (HR 2.28, P < .001) and PFS (HR 2.26, P < .001). When including pack-years as the covariate, ≥20 pack-years predicted a decreased effect-size for inferior OS and PFS.

Conclusions: For patients with HPV(+) OPSCC, active smoking at diagnosis is the most powerful covariate capturing smoking history to predict OS and PFS.
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http://dx.doi.org/10.1002/hed.26001DOI Listing
February 2020

Long-term complications and reconstruction failures in previously radiated breast cancer patients receiving salvage mastectomy with autologous reconstruction or tissue expander/implant-based reconstruction.

Breast J 2019 11 1;25(6):1071-1078. Epub 2019 Jul 1.

Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, Ohio.

Salvage mastectomy (SM) is the standard of care for patients with local recurrence (LR) after breast conservation therapy (BCT), often with immediate reconstruction. Complications of reconstruction are a concern for these patients, and long-term data are limited. We sought to compare rates of complications requiring re-operation (CRR) and reconstruction failure (RF) between autologous reconstruction (AR) and tissue expander/implant reconstruction (TE/I). Patients with locally recurrent breast cancer after BCT, treated with SM and immediate AR or TE/I between 2000 and 2008, were identified. CRR was defined as unplanned return to operating room for wound infection, dehiscence, necrosis (including flap, skin, or fat), hematoma, or hernia (for AR) and extrusion, leak, or capsular contracture (for TE/I). RF was defined as conversion to another reconstruction technique or to flat chest wall. This study included 103 patients with 107 reconstructions. Median follow-up was 6.6 years. CRR and RF were significantly higher with TE/I (n = 34) compared to AR (n = 73) at 5 years (50.9% vs 25.5%; P = 0.02) and (42.1% vs 5.8%; P < 0.001). On univariate analysis (UVA), TE/I (HR = 2.14; P = 0.02) and diabetes (HR = 5.10; P = 0.007) were significant predictors for CRR. On UVA, TE/I (HR = 7.30; P < 0.001) and older age at reconstruction (HR = 1.03; P = 0.003) were significant predictors for RF. In this population of previously irradiated patients, TE/I was associated with significantly higher CRR and RF. Complications continue to occur up to 10 years after TE/I. AR should be considered in appropriately selected patients, though TE/I may remain a reasonable option in patients without high-risk factors for surgical complications.
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http://dx.doi.org/10.1111/tbj.13428DOI Listing
November 2019

Second primary tumors in patients with a head and neck paraganglioma.

Head Neck 2019 09 25;41(9):3356-3361. Epub 2019 Jun 25.

Cleveland Clinic, Head & Neck Institute, Cleveland, Ohio.

Background: There are conflicting recommendations and possibly overuse of imaging for surveillance of second primary tumors for patients with a history of head and neck paraganglioma.

Methods: Retrospective cohort study of 234 adults with head and neck paragangliomas (1990-2010) followed for a mean of 7.5 ± 8.4 years.

Results: The rate of second paraganglioma was 1.7% after 5 years and 5.1% after 10 years, yielding an incidence of 6.65 per 1000 person-years. Only 1.3% of patients (2.59 per 1000 person-years) ever had a second paraganglioma in the chest, abdomen, or pelvis. Patients with a hereditary paraganglioma (hazard ratio [HR] = 4.84, 95% confidence interval [CI]: 1.52-15.43) or carotid body tumor (HR = 3.55, 95% CI: 1.15-10.99) were at greater risk.

Conclusions: The incidence rate of a second primary paragangliomas is low but increases with hereditary disease. These results question the utility of repeated imaging outside of the neck to screen for second paragangliomas.
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http://dx.doi.org/10.1002/hed.25849DOI Listing
September 2019

Long-Term Outcomes After Autologous or Tissue Expander/Implant-Based Breast Reconstruction and Postmastectomy Radiation for Breast Cancer.

Pract Radiat Oncol 2019 Nov 22;9(6):e497-e505. Epub 2019 Jun 22.

Taussig Cancer Institute, Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio.

Purpose: The toxicity profile of breast reconstruction with postmastectomy radiation therapy (PMRT) varies by technique and timing, and long-term data are limited. We compared rates of complications requiring reoperation (CRR) and reconstruction failure (RF) between immediate autologous reconstruction (I-AR), immediate tissue expander/implant reconstruction (I-TE/I), delayed autologous reconstruction (D-AR), and delayed tissue expander/implant reconstruction (D-TE/I) in patients receiving PMRT.

Methods And Materials: Patients who received autologous reconstruction (AR) or tissue expander/implant reconstruction (TE/I) and PMRT between 2000 to 2008 were included. Reconstruction was immediate if performed on the same day as mastectomy followed by PMRT (I-AR or I-TE/I) or delayed if after PMRT (D-AR and D-TE/I). CRR was defined as an unplanned return to the operating room for infection, dehiscence, necrosis, hematoma, or hernia (with AR) and extrusion, leak, or contracture (with TE/I). RF was defined as unplanned conversion to another reconstruction technique or to flat chest wall. Cumulative incidence of CRR and RF was calculated using Kaplan-Meier and compared using the log-rank test. Logistic regression was used to identify variables associated with CRR and RF.

Results: Two hundred four patients were included. Median follow-up was 8 years. There were 127 AR cases (63%) and 77 TE/I cases (38%). At 5 years, CRR was 18%, 38%, 34%, and 70% (P = .010) and RF was 4%, 22%, 7%, and 56% (P < .0001) for I-AR, I-TE/I, D-AR, and D-TE/I, respectively. On multivariate analysis, TE/I (hazard ratio [HR] 2.0; P = .011), body mass index ≥30 (HR 3.9; P = .002), and smoking (HR 2.7; P = .001) were significant predictors for CRR, and TE/I (HR 6.6; P < .0001), diabetes (HR 4.1; P = .044), and hypertension (HR 3.5; P = .005) were significant for RF. When excluding RF because of infection, the rate of RF was not significantly different among the 4 groups (P = .23).

Conclusions: With PMRT, TE/I reconstruction in the immediate and delayed setting is associated with higher CRR and RF compared with AR. Patient factors should guide selection of technique. Efforts to reduce rates of RF with TE/I should focus on minimizing risks for infection.
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http://dx.doi.org/10.1016/j.prro.2019.06.008DOI Listing
November 2019

Analysis of Process-Related Quality Metrics and Survival of Patients with Oral Cavity Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2019 09 7;161(3):450-457. Epub 2019 May 7.

1 Head and Neck Institute, The Cleveland Clinic, Cleveland, Ohio, USA.

Objective: To analyze the association of prior reported key quality metrics-neck dissection ≥18 nodes, radiation oncology referral for stage III/IV disease, unplanned surgery ≤14 days, and unplanned readmission ≤30 days-with disease-free survival (DFS) and overall survival (OS) in oral cavity cancer (OCC).

Study Design: A retrospective chart review.

Setting: A tertiary care center from 1995 to 2016.

Subjects And Methods: Data from patients with OCC who underwent primary surgery were studied. The association of quality metrics and pathology with DFS/OS was determined by Cox proportional hazards regression analysis.

Results: A total of 514 patients were included, and 398 (77.4%) underwent elective neck dissection. Key metrics were not associated with DFS on analysis, but higher pathologic stage and extracapsular extension (ECE) were. When stratified by stage, unplanned readmission within 30 days was associated with decreased survival on multivariate analysis (HR = 0.40; 95% CI, 0.20-0.85; = .02) for patients with clinical stage III or IV disease. ECE was associated with decreased survival among these patients as well. Neck dissection with ≤18 nodes (HR = 0.62; 95% CI, 0.44-0.86; = .004) and unplanned surgery within 14 days (HR = 0.56; 95% CI, 0.32-0.96; = .03) were associated with decreased survival on univariate analysis but not on multivariate analysis. ECE and higher-stage disease were associated with decreased OS on multivariate analysis.

Conclusion: In this study, aggressive pathology, rather than adherence to key quality metrics, was associated with lower DFS and OS among patients with OCC. More studies are needed to elucidate the association of quality metrics with survival.
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http://dx.doi.org/10.1177/0194599819845864DOI Listing
September 2019

Risk Factors for Progression Among Low-Grade Gliomas After Gross Total Resection and Initial Observation in the Molecular Era.

Int J Radiat Oncol Biol Phys 2019 08 22;104(5):1099-1105. Epub 2019 Apr 22.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio; Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Purpose: To identify risk factors for progression-free survival (PFS) in the molecular era among patients with low-grade glioma (LGG) who undergo gross total resection (GTR) followed by initial observation.

Methods And Materials: We reviewed patients with World Health Organization grade 2 LGG treated at a single institution. We included only those who underwent magnetic resonance imaging (MRI)-confirmed GTR followed by initial observation. Molecular classification was obtained at either the time of diagnosis or pathology review. Cox proportional hazards regression, the Kaplan-Meier method, and the log-rank test were used. P values <.05 were considered statistically significant.

Results: We included 144 patients who underwent MRI-confirmed GTR between 1994 and 2014 followed by initial observation. Median age was 29 years (interquartile range [IQR], 18-41), median tumor size was 2.7 cm (IQR, 1.8-4.0), and median follow-up was 81 months (IQR, 36-132). Molecular classification was 13% IDH-mutant 1p19q-codeleted; 21% IDH-mutant 1p19q-intact; 39% IDH1-R132H-wildtype; and 28% undetermined. For the entire cohort, 5- and 10-year PFS and overall survival were 71% and 53%, and 98% and 90%, respectively. On multivariate analysis, factors associated with worse PFS included increasing age at diagnosis (hazard ratio [HR], 1.05; 95% CI, 1.00-1.09; P = .03), increasing preoperative tumor size (HR, 1.07; 95% CI, 1.04-1.10; P < .0001), and IDH-mutant 1p19q-intact classification (HR, 3.18; 95% CI, 1.15-8.74, P = .025). Median PFS for patients with IDH-mutant 1p19q-codeleted, IDH-mutant 1p19q-intact, and IDH1-R132H-wildtype tumors were 113 months, 56 months, and not reached, respectively. Molecular classification was significantly associated with PFS (P < .0001) but not overall survival (P = .20).

Conclusions: Among patients with LGG who undergo MRI-confirmed GTR and initial observation in the molecular era, increasing age, increasing tumor size, and IDH-mutant 1p19q-intact classification are associated with worse PFS. Because tumor progression is associated with adverse health-related quality of life, these factors may aid clinicians and patients in the shared decision-making process regarding goals of surgery and timing of postoperative therapy. Further study is required to elucidate why IDH-mutant 1p19q-intact LGGs are at higher risk for early progression.
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http://dx.doi.org/10.1016/j.ijrobp.2019.04.010DOI Listing
August 2019

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

Eur Urol 2020 01 13;77(1):3-10. Epub 2019 Apr 13.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Background: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.

Objective: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).

Design, Setting, And Participants: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).

Outcome Measurements And Statistical Analysis: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.

Results And Limitations: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).

Conclusions: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.

Patient Summary: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
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http://dx.doi.org/10.1016/j.eururo.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521828PMC
January 2020
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