The contemporary treatment paradigm for jugular paraganglioma focuses on the preservation of neur... more The contemporary treatment paradigm for jugular paraganglioma focuses on the preservation of neurologic function. For this reason, non-invasive means of achieving tumor control with minimal morbidity have been adopted as first line therapeutic options. Conventional radiation therapy is utilized for large, inoperable tumors but carries a small risk of local tissue injury and must be delivered over several weeks. In contrast, stereotactic radiosurgery and radiotherapy, with steep radiation falloff gradients, permits the delivery of a high dose of focused radiation in a single treatment or hypofractionated fashion to arrest tumor growth with reduced collateral injury. In the absence of prior treatment, these modalities achieve tumor control rates of greater than 90% in most series. Radiosurgery for recurrent disease, or in an adjuvant fashion following subtotal tumor resection, has been demonstrated to yield similar tumor control while avoiding cranial nerve damage that may occur with attempts at gross total tumor resection. Patients may experience an attendant decrease in symptoms such as pulsatile tinnitus, making this an attractive treatment option when the risk associated with surgery is high.
Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma ... more Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma (ENB). Objective This study was aimed to investigate if planned adjuvant radiotherapy improves tumor control after complete margin negative resection of low Hyams' grade (1 or 2) ENB. Methods A retrospective review of patients with pathologically confirmed negative margin resection of Kadish's stage B or C and Hyams' grade 1 and 2 ENBs was conducted. Seventeen patients meeting the criteria were divided into the following two groups for cohort study: (1) those who underwent planned immediate postoperative adjuvant radiotherapy (IR group) and (2) those who did not (delayed radiotherapy [DR] group). Results The IR group included nine patients (Kadish's stage B in one and stage C in eight; Hyams' grade 1 in two and grade 2 in seven). Mean follow-up was 140.8 months. Seven patients (78%) had disease progression (DP) at a median of 88 months (four with cervical lymph node metastasis [CLNM], one with distant metastasis, and two with both local recurrence and CLNM). One patient experienced frontal lobe abscess. The DR group included eight patients (Kadish's stage B in six and stage C in two; all Hyams' grade 2). Mean follow-up was 123.3 months. Four (50%) patients who developed DP (all local recurrence) were salvaged with surgery and adjuvant radiotherapy at a median of 37.5 months. There was no statistically significant difference in DP rate (p = 0.23), time to DP (p = 0.26), or the local tumor control rate (p = 0.23). Conclusion In our limited cohort, immediate postoperative radiotherapy did not demonstrate superiority in tumor control, although risk of radiotherapy toxicity appears low.
OBJECTIVERadiation dose to the cochlea has been proposed as a key prognostic factor in hearing pr... more OBJECTIVERadiation dose to the cochlea has been proposed as a key prognostic factor in hearing preservation following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). However, understanding of the predictive value of cochlear dose on hearing outcomes following SRS for patients with non-VS tumors of the lateral skull base (LSB) is incomplete. The authors investigated rates of hearing loss following high-dose SRS in patients with LSB non-VS lesions compared with patients with VS.METHODSPatients with LSB meningioma or jugular paraganglioma and serviceable pretreatment hearing who underwent SRS treatment during 2007–2016 and received a modiolus dose > 5 Gy were included in a retrospective cohort study, along with a similarly identified control group of consecutive patients with sporadic VS.RESULTSSixteen patients with non-VS tumors and a control group of 43 patients with VS met study criteria. Serviceable hearing, defined as American Academy of Otololaryngology–Head and Neck Surgery class A/B, was maintained in 13 non-VS versus 23 VS patients (81% vs 56%, p = 0.07). All 3 instances of hearing loss in non-VS patients were observed in cerebellopontine angle (CPA) meningiomas. Non-VS with preserved hearing had a median modiolus dose of 6.9 Gy (range 5.7–19.2 Gy), versus 7.4 Gy (range 5.4–7.6 Gy) in those patients with post-SRS hearing loss (p = 0.53). Sporadic VS patients received an overall median modiolus point-dose of 6.8 Gy (range 5.4–11.7 Gy).CONCLUSIONSThe modiolus dose threshold of 5 Gy does not predict hearing loss in patients with non-VS tumors undergoing SRS, suggesting that dosimetric parameters derived from VS may not be applicable to this population. Differential rates of hearing loss appear to vary by pathology, with paragangliomas and petroclival meningiomas demonstrating decreased risk of hearing loss compared to CPA meningiomas that may directly compress the cochlear nerve similarly to VS.
OBJECTIVES To develop nomograms predicting overall survival (OS), freedom from locoregional recur... more OBJECTIVES To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively. RESULTS The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome. CONCLUSIONS We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.
PURPOSE Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival ~6 months... more PURPOSE Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival ~6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. PATIENT AND METHODS An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg IV every 3 weeks, combined with chemoradiotherapy [docetaxel/doxorubicin, 20 mg/m2 each IV weekly plus volumetric modulated arc therapy (VMAT)] was initiated as front-line therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month overall survival (OS) was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based upon a prior patient cohort treated similarly, but without pembrolizumab, the design was such that, if 6 month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. RESULTS Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation - one from pulmonary metastases, and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion - prompting study closure. CONCLUSION Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared to historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.
Otolaryngology-Head and Neck Surgery, Jul 14, 2020
We sought to determine the incidence and location of human papillomavirus (HPV)–associated anogen... more We sought to determine the incidence and location of human papillomavirus (HPV)–associated anogenital disease in women with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) via a retrospective cohort study with prospective contact to update history at Mayo Clinic in Rochester, Minnesota. Females undergoing treatment for nonmetastatic HPV-positive OPSCC from 2011 to 2019 were identified. Clinical history and outcomes were abstracted from medical records. Patients without documented anogenital history were contacted, consented, and administered a survey, and external records were requested and reviewed. Seventeen of 46 patients (37.0%) had a history of anogenital HPV-associated disease, and 16 of 17 (94.1%) required procedures to diagnose or treat HPV lesions. The cervix was the most common site (16/17, 94.1%). Procedures included colposcopy (n = 6), cervical excision (n = 3), cryotherapy (n = 4), and hysterectomy (n = 3). One case of fatal cervical carcinoma was noted, diagnosed 1 year following OPSCC. Three of 17 (17.6%) had HPV-related vulvovaginal disease, and 1 of 17 had anal disease. Patients with a history of HPV-positive OPSCC may be at elevated risk for HPV-associated anogenital disease.
International Forum of Allergy & Rhinology, Apr 25, 2022
ObjectiveEsthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epit... more ObjectiveEsthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival.Materials and methodsWe performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression‐free survival (PFS), and distant metastasis–free survival (DMFS) were reported.ResultsAmong 143 included patients, the 5‐year OS was 82.3% and the 5‐year PFS was 51.6%; 5‐year OS and PFS have improved in the modern era (2005–present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p &lt; 0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p &lt; 0.05). Positive margin status had a negative effect on PFS (p &lt; 0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p &lt; 0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p &lt; 0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p &lt; 0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p &lt; 0.05).ConclusionsPatients with low Hyams grade and mKadish stage have favorable 5‐year OS, PFS, and DMFS.
BackgroundWe aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during... more BackgroundWe aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC).MethodsRetrospective cohort at a tertiary center, 2006–2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC.ResultsAll 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post‐RT (N = 141): 0.68 (0.35) and long‐term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03–14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04–6.67, p = 0.04).ConclusionsLower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.Level of Evidence3
The contemporary treatment paradigm for jugular paraganglioma focuses on the preservation of neur... more The contemporary treatment paradigm for jugular paraganglioma focuses on the preservation of neurologic function. For this reason, non-invasive means of achieving tumor control with minimal morbidity have been adopted as first line therapeutic options. Conventional radiation therapy is utilized for large, inoperable tumors but carries a small risk of local tissue injury and must be delivered over several weeks. In contrast, stereotactic radiosurgery and radiotherapy, with steep radiation falloff gradients, permits the delivery of a high dose of focused radiation in a single treatment or hypofractionated fashion to arrest tumor growth with reduced collateral injury. In the absence of prior treatment, these modalities achieve tumor control rates of greater than 90% in most series. Radiosurgery for recurrent disease, or in an adjuvant fashion following subtotal tumor resection, has been demonstrated to yield similar tumor control while avoiding cranial nerve damage that may occur with attempts at gross total tumor resection. Patients may experience an attendant decrease in symptoms such as pulsatile tinnitus, making this an attractive treatment option when the risk associated with surgery is high.
Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma ... more Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma (ENB). Objective This study was aimed to investigate if planned adjuvant radiotherapy improves tumor control after complete margin negative resection of low Hyams' grade (1 or 2) ENB. Methods A retrospective review of patients with pathologically confirmed negative margin resection of Kadish's stage B or C and Hyams' grade 1 and 2 ENBs was conducted. Seventeen patients meeting the criteria were divided into the following two groups for cohort study: (1) those who underwent planned immediate postoperative adjuvant radiotherapy (IR group) and (2) those who did not (delayed radiotherapy [DR] group). Results The IR group included nine patients (Kadish's stage B in one and stage C in eight; Hyams' grade 1 in two and grade 2 in seven). Mean follow-up was 140.8 months. Seven patients (78%) had disease progression (DP) at a median of 88 months (four with cervical lymph node metastasis [CLNM], one with distant metastasis, and two with both local recurrence and CLNM). One patient experienced frontal lobe abscess. The DR group included eight patients (Kadish's stage B in six and stage C in two; all Hyams' grade 2). Mean follow-up was 123.3 months. Four (50%) patients who developed DP (all local recurrence) were salvaged with surgery and adjuvant radiotherapy at a median of 37.5 months. There was no statistically significant difference in DP rate (p = 0.23), time to DP (p = 0.26), or the local tumor control rate (p = 0.23). Conclusion In our limited cohort, immediate postoperative radiotherapy did not demonstrate superiority in tumor control, although risk of radiotherapy toxicity appears low.
OBJECTIVERadiation dose to the cochlea has been proposed as a key prognostic factor in hearing pr... more OBJECTIVERadiation dose to the cochlea has been proposed as a key prognostic factor in hearing preservation following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). However, understanding of the predictive value of cochlear dose on hearing outcomes following SRS for patients with non-VS tumors of the lateral skull base (LSB) is incomplete. The authors investigated rates of hearing loss following high-dose SRS in patients with LSB non-VS lesions compared with patients with VS.METHODSPatients with LSB meningioma or jugular paraganglioma and serviceable pretreatment hearing who underwent SRS treatment during 2007–2016 and received a modiolus dose &gt; 5 Gy were included in a retrospective cohort study, along with a similarly identified control group of consecutive patients with sporadic VS.RESULTSSixteen patients with non-VS tumors and a control group of 43 patients with VS met study criteria. Serviceable hearing, defined as American Academy of Otololaryngology–Head and Neck Surgery class A/B, was maintained in 13 non-VS versus 23 VS patients (81% vs 56%, p = 0.07). All 3 instances of hearing loss in non-VS patients were observed in cerebellopontine angle (CPA) meningiomas. Non-VS with preserved hearing had a median modiolus dose of 6.9 Gy (range 5.7–19.2 Gy), versus 7.4 Gy (range 5.4–7.6 Gy) in those patients with post-SRS hearing loss (p = 0.53). Sporadic VS patients received an overall median modiolus point-dose of 6.8 Gy (range 5.4–11.7 Gy).CONCLUSIONSThe modiolus dose threshold of 5 Gy does not predict hearing loss in patients with non-VS tumors undergoing SRS, suggesting that dosimetric parameters derived from VS may not be applicable to this population. Differential rates of hearing loss appear to vary by pathology, with paragangliomas and petroclival meningiomas demonstrating decreased risk of hearing loss compared to CPA meningiomas that may directly compress the cochlear nerve similarly to VS.
OBJECTIVES To develop nomograms predicting overall survival (OS), freedom from locoregional recur... more OBJECTIVES To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively. RESULTS The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome. CONCLUSIONS We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.
PURPOSE Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival ~6 months... more PURPOSE Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival ~6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. PATIENT AND METHODS An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg IV every 3 weeks, combined with chemoradiotherapy [docetaxel/doxorubicin, 20 mg/m2 each IV weekly plus volumetric modulated arc therapy (VMAT)] was initiated as front-line therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month overall survival (OS) was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based upon a prior patient cohort treated similarly, but without pembrolizumab, the design was such that, if 6 month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. RESULTS Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation - one from pulmonary metastases, and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion - prompting study closure. CONCLUSION Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared to historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.
Otolaryngology-Head and Neck Surgery, Jul 14, 2020
We sought to determine the incidence and location of human papillomavirus (HPV)–associated anogen... more We sought to determine the incidence and location of human papillomavirus (HPV)–associated anogenital disease in women with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) via a retrospective cohort study with prospective contact to update history at Mayo Clinic in Rochester, Minnesota. Females undergoing treatment for nonmetastatic HPV-positive OPSCC from 2011 to 2019 were identified. Clinical history and outcomes were abstracted from medical records. Patients without documented anogenital history were contacted, consented, and administered a survey, and external records were requested and reviewed. Seventeen of 46 patients (37.0%) had a history of anogenital HPV-associated disease, and 16 of 17 (94.1%) required procedures to diagnose or treat HPV lesions. The cervix was the most common site (16/17, 94.1%). Procedures included colposcopy (n = 6), cervical excision (n = 3), cryotherapy (n = 4), and hysterectomy (n = 3). One case of fatal cervical carcinoma was noted, diagnosed 1 year following OPSCC. Three of 17 (17.6%) had HPV-related vulvovaginal disease, and 1 of 17 had anal disease. Patients with a history of HPV-positive OPSCC may be at elevated risk for HPV-associated anogenital disease.
International Forum of Allergy & Rhinology, Apr 25, 2022
ObjectiveEsthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epit... more ObjectiveEsthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival.Materials and methodsWe performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression‐free survival (PFS), and distant metastasis–free survival (DMFS) were reported.ResultsAmong 143 included patients, the 5‐year OS was 82.3% and the 5‐year PFS was 51.6%; 5‐year OS and PFS have improved in the modern era (2005–present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p &lt; 0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p &lt; 0.05). Positive margin status had a negative effect on PFS (p &lt; 0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p &lt; 0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p &lt; 0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p &lt; 0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p &lt; 0.05).ConclusionsPatients with low Hyams grade and mKadish stage have favorable 5‐year OS, PFS, and DMFS.
BackgroundWe aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during... more BackgroundWe aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC).MethodsRetrospective cohort at a tertiary center, 2006–2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC.ResultsAll 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post‐RT (N = 141): 0.68 (0.35) and long‐term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03–14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04–6.67, p = 0.04).ConclusionsLower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC.Level of Evidence3
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