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BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).
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Neoplasias Encefálicas , Radiocirurgia , Humanos , Estudos Retrospectivos , Radiocirurgia/métodos , Estudos Prospectivos , Resultado do Tratamento , Neoplasias Encefálicas/secundário , Necrose/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
OBJECTIVE: The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). METHODS: The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. RESULTS: The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). CONCLUSIONS: Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.
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Hipopituitarismo , Neoplasias Hipofisárias , Masculino , Humanos , Feminino , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Hipófise , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Hipopituitarismo/etiologia , CefaleiaRESUMO
PURPOSE: In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether 18F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS). METHODS: Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus 18F-DOPA PET defined tumor. RESULTS: Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing 18F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed. CONCLUSION: 18F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.
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Neoplasias Encefálicas , Glioma , Reirradiação , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Di-Hidroxifenilalanina/análogos & derivados , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Reirradiação/métodosRESUMO
INTRODUCTION: Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. METHODS: A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. RESULTS: Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75-43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16-23.75 months). The median prescription isodose volume was 1.85 cm3 (IQR, 1.85-7.02 cm3); median tumor margin dose was 18 Gy (IQR 14-20 Gy); and median isocenters was 2 (range 1-13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75-53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25-30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. DISCUSSION/CONCLUSION: This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.
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Neoplasias Encefálicas , Tumores Neuroectodérmicos Primitivos , Radiocirurgia , Neoplasias Encefálicas/cirurgia , Pré-Escolar , Humanos , Lactente , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Tumores Neuroectodérmicos Primitivos/radioterapia , Tumores Neuroectodérmicos Primitivos/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: Accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) are treatment options for early-stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI. METHODS: Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS) or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI (67) and participated in a PRO questionnaire. The linear analog scale assessment (LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale (BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and functional status, and breast cosmesis. Comparisons of PROs were performed using t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression methods. RESULTS: Median follow-up from completion of radiotherapy and questionnaire completion was 13.3 months. There was no significant difference in QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups (p > 0.05). No factors were found to be predictive of overall QoL on regression analysis. BCTOS health-related QoL scores were similar between treatment groups (p = 0.52).The majority of APBI and WBI patients reported excellent/good breast cosmesis, 88.5% versus 93.7% (p = 0.37). Skin color change (p = 0.011) and breast elevation (p = 0.01) relative to baseline were more common in the group receiving WBI. CONCLUSIONS: APBI and WBI were both associated with favorable patient-reported outcomes in early follow-up. APBI resulted in a lesser degree of patient-reported skin color change and breast elevation relative to baseline.
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Braquiterapia/efeitos adversos , Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Carcinoma Intraductal não Infiltrante/radioterapia , Adulto , Idoso , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Resultado do TratamentoRESUMO
INTRODUCTION: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. METHODS: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression. RESULTS: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab. CONCLUSIONS: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.
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Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Ipilimumab/uso terapêutico , Melanoma/patologia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Ipilimumab/efeitos adversos , Masculino , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Purpose: To assess any correlation between swallowing dysfunction and radiation dose to 5 subregions of the larynx. Methods and Materials: A cohort of 136 patients with head and neck cancer, treated with either photon or proton radiation therapy, was assessed using an endpoint of patient-reported swallowing scores, evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 survey, within 1 month after treatment. Five subregions of the larynx were contoured, and dosimetric metrics were extracted for each subregion as well as the total larynx. Univariate and multivariate logistic regression statistical analyses were used to determine statistical correlation with the dose metrics and clinical variables. Univariate regression models were statistically compared using a non-nested model test. Results: Under univariate analysis, unilateral versus bilateral nodal irradiation (P = .004), concurrent chemotherapy (P = .007), and surgery (P = .015) were statistically significant predictors of poor swallowing score. Unilateral versus bilateral irradiation was statistically significant under multivariate analysis (P = .039). The epiglottis was the most predictive subregion of swallowing score, with a majority (21 of 25) of dosimetric variables being identified as statistically significant. The maximum dose to the epiglottis was the most significant dosimetric variable tested for poor swallowing score in both univariate (P = .003) and multivariate (P = .051) analyses. Comparison of univariate models indicated a general preference for epiglottic variables with the mean dose to the epiglottis being preferred at a statistically significant level in many cases. Conclusions: These results show the relatively increased sensitivity of the epiglottis compared with the rest of the larynx when considering patient-reported decrements in quality-of-life swallowing score and support both the inclusion of the epiglottis in standard larynx contours and the assessment of the epiglottis dose during plan evaluation. Our data suggest that keeping the mean and max doses to the epiglottis <20 to 37 Gy and <53 to 60 Gy, respectively, will reduce swallowing difficulties.
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OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Herein, the authors examine the oncological outcomes of patients with positive margins after primary resection of ONB, with the aim of determining predictors of disease progression and patterns of recurrence. METHODS: The authors performed an institutional review of 25 patients with positive-margin ONB after resection. Cox survival analyses were used to determine any statistically significant predictors of worse progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 93 patients who were diagnosed with ONB were identified, of whom 25 patients had positive margins following their primary resection. Eleven (44%) had a delayed finding of positive margins that were initially negative in the operating room but returned as positive on final pathology. Four patients had subtotal resection (STR), whereas the remaining patients underwent gross-total resection. Twenty-four patients received adjuvant radiotherapy (96%), and 15 additionally received adjuvant chemotherapy (60%). Fourteen patients (56%) experienced recurrence/progression at a median time of 35 months following resection (IQR 19-70 months). Local recurrence occurred in 10 patients (40%), regional in 9 (36%), and distant metastasis in 2 (8%). In Cox survival analyses, the 5-year PFS and OS were 55.1% and 79.2%, respectively. Kadish stage D was predictive of worse PFS in univariate (hazard ratio [HR] 15.67, 95% CI 3.38-72.61, p < 0.001) and multivariate (HR 15.46, 95% CI 1.45-164.91, p = 0.023) analyses. Hyams grade, adjuvant chemotherapy, and primary radiotherapy were not associated with PFS. Furthermore, Kadish stage D and STR were predictive of worse OS in univariate analysis (HR 12.64, 95% CI 2.03-78.86, p = 0.007; HR 7.31, 95% CI 1.45-36.84, p = 0.016; respectively). However, local and regional recurrence was not associated with worse OS. CONCLUSIONS: Approximately half of patients with positive-margin ONB may experience disease recurrence. Patients with an advanced disease stage (Kadish D) may have a higher likelihood of developing recurrence/progression. Furthermore, patients with tumor burden following resection (STR and Kadish D) may have worse OS. However, in positive-margin ONB with no gross disease following initial resection, the presence of disease recurrence does not significantly alter survival when receiving salvage therapy.
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Objectives: To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy. Methods: We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated. Results: DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation. Conclusions: Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.
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Treatment of squamous cell carcinoma of the tonsil involves primary radiation therapy (RT) or surgical resection. Historically, if RT was the primary or adjuvant treatment modality, most of the bilateral retropharyngeal lymph nodes (RPLNs) were treated electively with a therapeutic dose for subclinical disease, regardless of whether radiographically pathologic lymph nodes were seen on initial diagnostic imaging. De-escalation strategies include the incorporation of transoral surgery with the goal to either eliminate or reduce the dose of adjuvant RT or chemotherapy. Transoral surgery does not include elective removal of the RPLNs, and no guideline or outcome paper recommends adjuvant RT specifically to electively treat RPLNs. In this Topic Discussion, we discuss pertinent literature and suggest management decisions. The management decisions discussed in this Topic Discussion pertain to only tonsillar primaries and not those of the soft palate or base of the tongue.
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BACKGROUND: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Testing for plasma tumor tissue modified viral (TTMV)-HPV DNA has emerged as a biomarker strategy for post-treatment surveillance to identify recurrent disease. We aimed to understand the prognostic and predictive potential of TTMV-HPV DNA when monitoring patients who had developed recurrent or metastatic (R/M) HPV+OPSCC. METHODS: This retrospective observational cohort study included 80 patients from 4 academic centers with R/M HPV+OPSCC if they had ≥ 1 plasma TTMV-HPV DNA test obtained at any point during their R/M disease course. Physician-reported clinical data and treatment history were captured in a centralized database, along with investigator-assessed response to therapy and survival. Descriptive statistics and non-parametric tests of association were employed along with survival analyses (Kaplan-Meier method). RESULTS: Sixteen (20 %) patients had ≥ 5 test results over time. Consecutive TTMV-HPV DNA tests were performed a median of 73 days apart. Median TTMV-HPV DNA scores were higher with an increasing per-patient number of metastatic sites (<2 vs. 2+; p < 0.01). Score changes over time were influenced by R/M treatment modality and became undetectable in 67 % (12/18) of patients who achieved a complete response to R/M therapy. Patients with detectable scores at last follow-up had significantly worse survival compared with those who were undetectable (log-rank test, p < 0.01). CONCLUSIONS: TTMV-HPV DNA appears useful as a prognostic tool for monitoring response to therapy in the R/M setting. In the future, TTMV-HPV DNA could be explored as an exploratory clinical trial endpoint in the metastatic setting.
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OBJECTIVES: Blood-based multi-cancer early detection (MCED) tests are now commercially available. However, there are currently no consensus guidelines available for head and neck cancer (HNC) providers to direct work up or surveillance for patients with a positive MCED test. We seek to describe cases of patients with positive MCED tests suggesting HNC and provide insights for their evaluation. METHODS: Retrospective chart review of patients referred to Otolaryngology with an MCED result suggesting HNC. Patients enrolled in prospective MCED clinical trials were excluded. Cancer diagnoses were confirmed via frozen-section pathology. RESULTS: Five patients were included (mean age: 69.2 years, range 50-87; 4 male) with MCED-identified-high-risk for HNC or lymphoma. Only patient was symptomatic. After physical exam and follow-up head and neck imaging, circulating tumor HPV DNA testing, two patients were diagnosed with p16 + oropharyngeal squamous cell carcinomas and underwent appropriate therapy. A third patient had no evidence of head and neck cancer but was diagnosed with sarcoma of the thigh. The remaining two patients had no evidence of malignancy after in-depth workup. CONCLUSIONS: In this retrospective study, 2 of 5 patients referred to Otolaryngology with a positive MCED result were diagnosed with HPV + oropharyngeal squamous cell carcinoma. We recommend that positive HNC MCED work up include thorough head and neck examination with flexible laryngoscopy and focused CT or MRI imaging. Given the potential for inaccurate MCED tissue of origin classification, PET/CT may be useful in specific situations. For a patient with no cancer identified, development of clear guidelines is warranted.
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Detecção Precoce de Câncer , Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Detecção Precoce de Câncer/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Encaminhamento e ConsultaRESUMO
Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.
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PURPOSE: The COVID-19 pandemic led to rapid expansion of telemedicine. The implications of telemedicine have not been rigorously studied in radiation oncology, a procedural specialty. This study aimed to evaluate the characteristics of in-person patients (IPPs) and virtual patients (VPs) who presented to a large cancer center before and during the pandemic and to understand variables affecting likelihood of receiving radiotherapy (yield) at our institution. METHODS: A total of 17,915 patients presenting for new consultation between 2019 and 2021 were included, stratified by prepandemic and pandemic periods starting March 24, 2020. Telemedicine visits included video and telephone calls. Area deprivation indices (ADIs) were also compared. RESULTS: The overall population was 56% male and 93% White with mean age of 63 years. During the pandemic, VPs accounted for 21% of visits, were on average younger than their in-person (IP) counterparts (63.3 years IP v 62.4 VP), and lived further away from clinic (215 miles IP v 402 VP). Among treated VPs, living closer to clinic was associated with higher yield (odds ratio [OR], 0.95; P < .001). This was also seen among IPPs who received treatment (OR, 0.96; P < .001); however, the average distance from clinic was significantly lower for IPPs than VPs (205 miles IP v 349 VP). Specialized radiotherapy (proton and brachytherapy) was used more in VPs. IPPs had higher ADI than VPs. Among VPs, those treated had higher ADI (P < .001). CONCLUSION: Patient characteristics and yield were significantly different between IPPs and VPs. Telemedicine increased reach to patients further away from clinic, including from rural or health care-deprived areas, allowing access to specialized radiation oncology care. Telemedicine has the potential to increase the reach of other technical and procedural specialties.
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Radioterapia (Especialidade) , Telemedicina , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Pandemias , Instituições de Assistência Ambulatorial , Ifosfamida , Encaminhamento e ConsultaRESUMO
Background: This study aimed to determine whether proton craniospinal irradiation (CSI) decreased the dose to normal tissue and resulted in less toxicity than photon CSI for adult patients. Methods: This single-institution retrospective analyzed differences in radiation doses, acute toxicity, and cost between proton and CSI for adult medulloblastoma patients. Results: Of 39 total patients, 20 were treated with photon CSI prior to 2015, and 19 were treated with proton CSI thereafter. Median age was 28 years (range 18-66). The molecular subtype was most commonly sonic hedgehog (68%). Patients most commonly received 36 Gy CSI in 20 fractions with a boost to 54-55.8 Gy (92%). Proton CSI delivered significantly lower mean doses to cochleae, lacrimal glands, lens, parotid glands, pharyngeal constrictors, esophagus, lungs, liver, and skin (all Pâ <â .001). Patients receiving proton CSI had significantly lower rates of acute dysphagia of any grade (5% versus 35%, Pâ =â .044) and decreased median weight loss during radiation (+1.0 versus -2.8 kg, Pâ =â .011). Weight loss was associated with acute hospitalization (Pâ =â .009). Median follow-up was 2.9 and 12.9 years for proton and photon patients, respectively, limiting late toxicity and outcome comparisons. At the last follow-up, 5 photon patients had died (2 of progressive disease, 3 without recurrence ages 41-63) and 21% had experienced major cardiovascular events. At 10 years, 89% were alive and 82% were recurrence free. Conclusions: This study demonstrates dosimetric improvements with proton CSI, potentially leading to decreased acute toxicity including dysphagia and weight loss during treatment.
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Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer. Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics. Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives. Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review.
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BACKGROUND: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient's quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. METHODS: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. RESULTS: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. CONCLUSIONS: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.
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OBJECTIVE: Metastasis to the pituitary gland is uncommon. With life expectancy after cancer diagnosis improving, we sought to understand the effects of treating pituitary metastasis in the modern era of advanced cancer treatment. METHODS: Patients who had been diagnosed with, and treated for, pituitary metastasis from 2000 to 2021 were retrospectively analyzed. RESULTS: A total of 48 patients were identified, of whom 23 (48%) were women. The most common primary cancer was the lung (n = 23; 48%), followed by the breast (n = 9; 19%). Of the 48 patients, 29 (60%) had had hypopituitarism and 12 (25%), visual field deficits. Twenty-seven patients (56%) had had solitary pituitary metastasis, with no evidence of other intracranial metastatic lesions. Of the 48 patients, 14 (29%) had undergone surgery and 20 (42%) had undergone standalone radiation therapy (preceded by biopsy for 3). After surgery and/or radiation therapy, the visual field deficits had improved in 6 patients, hypopituitarism had improved in 4 patients, and hypopituitarism had occurred in 3 patients. The median overall survival (OS) was 12 months (interquartile range, 3.0-28 months). Multivariate analysis showed nonsolitary pituitary metastasis (hazard ratio, 2.8; 95% confidence interval, 1.5-5.5; P = 0.0021) and no surgery or radiation therapy (hazard ratio, 2.08; 95% confidence interval, 1.04-4.15; P = 0.038) were associated with OS. For those with solitary pituitary metastasis, the patients who had undergone surgery and/or radiation therapy had had better 1-year OS than patients who had not received either (P = 0.03). In contrast, for patients with nonsolitary pituitary metastasis, those who had undergone standalone radiation therapy had had better 1-year OS than the patients who had not received either (P = 0.03). CONCLUSIONS: In the selected population, metastasis-directed therapy was associated with improved OS. Either correct patient selection for additional therapy or surgery and/or radiation therapy directly benefited patients' OS.
Assuntos
Hipopituitarismo , Neoplasias Hipofisárias , Humanos , Feminino , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Hipófise , Hipopituitarismo/etiologia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/radioterapiaRESUMO
OBJECTIVE: We aim to explore the prognostic value of tumor-infiltrating lymphocytes (TILs) in the primary tumor and metastatic lymph nodes of patients with HPV(+)OPSCC. We hypothesize that TILS density at both sites is associated with disease-free survival in HPV(+)OPSCC. STUDY DESIGN: Matched case-control study among HPV(+)OPSCC patients who underwent intent-to-cure surgery. Cases developed locoregional or distant recurrence. Controls were matched based on age, sex, pathologic T, N, and overall stage, year of surgery, type of adjuvant treatment received, and the Adult Comorbidity Evaluation-27 (ACE-27) score. SETTING: Single tertiary care center, May 2007 to December 2016. METHODS: Tumoral TILs (tTILs) density was defined as % TILs; stromal TILs (sTILs) density was defined as absent/sparse or moderate/dense crowding. Associations between TILs and time to disease progression were assessed using Cox regression models. RESULTS: Forty-four case-control pairs (N = 88) were included: 42 (48%) AJCC pStage I, 39 (44%) pStage II, and 7 (8%) pStage III. tTILs density ≥10% (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.17-0.99, p = .048) and a moderate/dense sTILs density (HR 0.21, 95% CI 0.06-0.75, p = .016) in the primary tumor were significantly associated with decreased risk of progression. TILs density in the lymph node was associated with decreased risk of progression but did not reach statistical significance. The tTILs and sTILs density correlated strongly between the primary tumor and lymph node. Concordance between the pathologists' was moderate (60%-70%). CONCLUSIONS: In HPV(+)OPSCC, a higher density of tumoral and stromal TILs in the primary tumor and possibly the lymph node may predict a lower risk of disease progression.
Assuntos
Carcinoma , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Adulto , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Linfócitos do Interstício Tumoral , Estudos de Casos e Controles , Prognóstico , Progressão da Doença , Carcinoma/patologiaRESUMO
OBJECTIVE: Failure to recognize symptoms of non-human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(-)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(-)OPSCC. METHODS: Retrospective review at a tertiary care center. Patients with HPV(-)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care. RESULTS: Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32-127 days), with a median latency of 30 days (IQR = 12-61 days) from symptom onset to first presentation and 19.5 days (IQR = 4-46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis. CONCLUSIONS: Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(-)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(-)OPSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1394-1401, 2023.