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1.
Oncoimmunology ; 10(1): 1863631, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33643689

RESUMO

We conducted a phase I dose-escalation trial of radiation with ipilimumab in patients with melanoma with ≥2 metastatic lesions. Here, we report the final full clinical analysis. Patients received RT (6 or 8 Gy x 2 or 3 doses) to a single lesion followed by 4 cycles of ipilimumab. The primary endpoint was maximum tolerated dose of RT, and secondary endpoint was response at non-radiated sites. Twenty-two patients with treatment-naïve (n = 11) or treatment-refractory (n = 11) Stage IV melanoma were enrolled. There were 31 treatment-related adverse events (AEs), of which 16 were deemed immune-related. Eleven patients had grade 3 AEs (no grade 4/5). There were no dose-limiting toxicities related to the radiation/ipilimumab combination. Five of 22 patients (22.7%, 95% CI 7.8-45.4%) had partial response as best response and three (13.6%) had stable disease. Median overall survival was 10.7 months (95% CI, 4.9 months to not-estimable) and median progression-free survival 3.6 months (95% CI, 2.9 months to 7.8 months). Seven patients were still alive at the time of last follow-up (median follow-up 89.2 months), most of whom received pembrolizumab after progression. Radiotherapy followed by ipilimumab was well tolerated and yielded a response rate that compares favorably to the objective response rate with ipilimumab alone. Furthermore, 32% of patients are long-term survivors, most of whom received pembrolizumab. Based on these results, the recommended dose that was used in subsequent Phase 2 trials was 8 Gy x 3 doses. Clinical Trial Registration: NCT01497808 (www.clinicaltrials.gov).

2.
Laryngoscope ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570180

RESUMO

OBJECTIVES: Primary orbital melanoma (POM) is a rare disease with limited data on survival and best treatment practices. Here we utilize the National Cancer Database (NCDB) to determine the overall survival (OS) and covariates that influence mortality. STUDY DESIGN: Retrospective cohort study. METHODS: All patients diagnosed with POM from 2004 to 2016 were identified in the NCDB. Patient and oncologic data were analyzed using the Kaplan-Meier method and multivariate models for the primary outcome of OS. RESULTS: A total of 129 patients were identified. Median OS was 36.9 months (95% confidence interval [CI] 24.1-78.7 months) with mean 5-year survival of 42.0% (CI 33.2%-53.2%). Treatments received included surgery alone (43.4%), radiation alone (23.3%), and surgery followed by radiation (20.2%). The multivariate model demonstrated an increased risk of death associated with age over 80 years (hazard ratio [HR] 3.41, CI 1.31-8.86, P = .012), a Charlson-Deyo comorbidity score of 2 or greater (HR 5.30, CI 1.87-15.03, P = .002), and no treatment (HR 2.28, CI 1.03-5.06, P = .042). For every 1 cm increase in tumor size, there was an increased risk of death (HR 1.06, CI 1.00-1.13, P = .039). When compared to surgery alone, no other treatment modality had an effect on OS. CONCLUSIONS: This study leveraged multiyear data from the NCDB to provide prognostic and demographic information on the largest known cohort of POM cases. Increased age, increased comorbidities, not receiving treatment, and larger tumor size were associated with increased mortality. There was no clear survival advantage for specific treatments. LEVEL OF EVIDENCE: IV Laryngoscope, 2021.

3.
Head Neck ; 43(4): 1128-1141, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33325579

RESUMO

BACKGROUND: Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS). METHODS: Three-hundred and sixty-four patients with treatment-naïve, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared. RESULTS: The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3-year distant metastasis rates (8% vs 4%, P = .56) or worse 3-year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged. CONCLUSIONS: Patients with HPV-associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates.

4.
Ann Surg Oncol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230747

RESUMO

BACKGROUND: Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear. PATIENTS AND METHODS: Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates. RESULTS: Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20). CONCLUSIONS: In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.

5.
J Natl Cancer Inst ; 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32294209

RESUMO

BACKGROUND: Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS: Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was pre-specified. The primary outcome was overall survival (OS) and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous (IV) steroids. All statistical tests were two-sided. RESULTS: There were 568 patients in our database, of which 114 received antibiotics prior to ICI. 35.9% of patients had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.27-2.57, p<.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR 2.78, 95% CI 1.31-5.87, p=.007). When limited to only patients who received adjuvant ICI (N = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR 4.84, 95% CI 1.09-21.50, p=.04). The antibiotic group had a greater incidence of colitis (HR 2.14, 95% CI 1.02-4.52, p=.046). CONCLUSION: Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.

6.
Otolaryngol Head Neck Surg ; 162(6): 816-817, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32312163

RESUMO

The impact of the coronavirus disease 2019 (COVID-19) pandemic on the management of head and neck cancer must be addressed. Immediate measures to reduce transmission rates and protect patients and providers take priority and necessitate some delays in care, particularly for patients with mild symptoms or less aggressive cancers. However, strict guidelines have yet to be developed, and many unintentional delays in care are to be expected based on the magnitude of the looming public health crisis. The medical complexity of head and neck cancer management may lead to prolonged delays that worsen treatment outcomes. Therefore, those caring for patients with head and neck cancer must take action to reduce these negative impacts as the country rallies to overcome the challenges posed by this pandemic.


Assuntos
Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Neoplasias de Cabeça e Pescoço/terapia , Pandemias/prevenção & controle , Segurança do Paciente , Pneumonia Viral/prevenção & controle , Gerenciamento Clínico , Surtos de Doenças/estatística & dados numéricos , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pandemias/estatística & dados numéricos , Medição de Risco , Estados Unidos , Populações Vulneráveis/estatística & dados numéricos
7.
Head Neck ; 42(6): 1131-1136, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32298006

RESUMO

BACKGROUND AND METHODS: There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID-19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life-threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. RESULTS: After careful consideration of the options, we took different approaches in the care of these two patients. CONCLUSIONS: Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immunocompromised patients. We provide some general principles to help guide patient management during the current pandemic.


Assuntos
Tratamento Conservador/métodos , Infecções por Coronavirus/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Hospedeiro Imunocomprometido , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Tempo para o Tratamento/organização & administração , Adulto , Tomada de Decisão Clínica , Controle de Doenças Transmissíveis/métodos , Gerenciamento Clínico , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Comunicação Interdisciplinar , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Segurança do Paciente , Medição de Risco , Amostragem , Fatores de Tempo , Estados Unidos , Prega Vocal/patologia , Prega Vocal/cirurgia
8.
Oncologist ; 25(2): e381-e385, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32043765

RESUMO

Management of melanoma has been revolutionized by the use of immune checkpoint inhibitors. Immune system changes associated with aging may affect the efficacy of immune-based therapies. Using the National Cancer Database, we evaluated the impact of age on the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. We identified 11,944 patients from 2011-2015, of whom 25% received immunotherapy. Older (≥60 years), compared with younger, patients were less likely to receive immunotherapy (odds ratio, 0.69; 95% confidence interval [CI], 0.61-0.78; p < .001). Immunotherapy was associated with a survival benefit in both younger and older patients (<60 years: hazard ratio [HR], 0.64; 95% CI, 0.57-0.72; p < .001; ≥60 years: HR, 0.55; 95% CI, 0.50-0.60; p < .001). Importantly, there was a statistically significant interaction between age and survival with immunotherapy, where a greater benefit was observed for older patients (pinteraction = 0.013). Further work studying the age-related response to immunotherapy is warranted.

9.
Br J Radiol ; 93(1107): 20190638, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31845816

RESUMO

OBJECTIVE: To evaluate dosimetric consequences of inter-fraction setup variation and anatomical changes in patients receiving multifield optimised (MFO) intensity modulated proton therapy for post-operative oropharyngeal (OPC) and oral cavity (OCC) cancers. METHODS: Six patients receiving MFO for post-operative OPC and OCC were evaluated. Plans were robustly optimised to clinical target volumes (CTVs) using 3 mm setup and 3.5% range uncertainty. Weekly online cone beam CT (CBCT) were performed. Planning CT was deformed to the CBCT to create virtual CTs (vCTs) on which the planned dose was recalculated. vCT plan robustness was evaluated using a setup uncertainty of 1.5 mm and range uncertainty of 3.5%. Target coverage, D95%, and hotspots, D0.03cc, were evaluated for each uncertainty along with the vCT-calculated nominal plan. Mean dose to organs at risk (OARs) for the vCT-calculated nominal plan and relative % change in weight from baseline were evaluated. RESULTS: Robustly optimised plans in post-operative OPC and OCC patients are robust against inter-fraction setup variations and range uncertainty. D0.03cc in the vCT-calculated nominal plans were clinically acceptable across all plans. Across all patients D95% in the vCT-calculated nominal treatment plan was at least 100% of the prescribed dose. No patients lost ≥10% weight from baseline. Mean dose to the OARs and max dose to the spinal cord remained within tolerance. CONCLUSION: MFO plans in post-operative OPC and OCC patients are robust to inter-fraction uncertainties in setup and range when evaluated over multiple CT scans without compromising OAR mean dose. ADVANCES IN KNOWLEDGE: This is the first paper to evaluate inter-fraction MFO plan robustness in post-operative head and neck treatment.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/radioterapia , Neoplasias Orofaríngeas/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Neoplasias Orofaríngeas/diagnóstico por imagem , Projetos Piloto , Cuidados Pós-Operatórios , Estudos Retrospectivos , Medula Espinal/efeitos da radiação , Incerteza
10.
Int J Radiat Oncol Biol Phys ; 106(4): 725-732, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31785337

RESUMO

PURPOSE: This trial tested the safety and efficacy of a novel, deintensified radiation therapy (RT) approach after initial surgical resection for patients with human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS: This single-arm phase 2 prospective clinical trial enrolled 60 patients with stage pT1-pT2 N1-3 HPV-associated OPSCC treated with transoral robotic surgery (TORS) and selective neck dissection at a single institution between May 2014 and September 2017. Patients had favorable features at the primary site (negative surgical margins ≥2 mm, no perineural invasion, and no lymphovascular invasion) but required adjuvant therapy based on lymph node involvement. Surgeries were all performed at a high-volume head and neck cancer center with expertise in TORS. Patients received postoperative RT to at-risk areas in the involved neck (60-66 Gy) and uninvolved neck (54 Gy). The resected primary site was treated as an active avoidance structure in the treatment planning of postoperative RT. Concurrent chemotherapy was administered for patients with extranodal extension. RESULTS: Median follow-up of the 60 patients enrolled was 2.4 years (range, 8.5-53.8 months). A single patient recurred at the primary site, for 2-year local control of 98.3%. One patient (1.7%) developed a regional neck recurrence, and 2 patients (3.3%) developed distant metastases. Measured 2-year local recurrence-free survival was 97.9% (95% confidence interval, 86.1%-99.7%). Overall survival was 100% at the time of analysis. The mean radiation dose to the primary site was 36.9 Gy (standard deviation, 10.3 Gy). Two patients (3.3%) experienced late soft tissue necrosis in the primary site surgical bed that resolved within 2 months. Feeding tube dependence rates were 0% during RT, 3.3% temporarily during follow-up, and 0% at last follow-up. CONCLUSIONS: Deintensified postoperative RT that avoids the resected primary tumor site and targets only the at-risk neck after TORS for selected patients with HPV-associated OPSCC may be safe and is worthy of further study.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/virologia , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Papillomaviridae/fisiologia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
11.
J Immunother ; 43(1): 8-15, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31498180

RESUMO

The effect of health insurance on management and outcomes in melanoma is unclear. Using the National Cancer Database (NCDB), we evaluated the effect of insurance on (1) stage at diagnosis, (2) receipt of immunotherapy, and (3) overall survival (OS) among patients with melanoma. We included patients with stage I-IV melanoma diagnosed from 2011 to 2015. Patients were stratified by age (below 65 vs. 65 y or above) and insurance (commercial, Medicare, Medicaid and uninsured). We evaluated the association between insurance and (1) stage at diagnosis (stage I-III vs. IV) and (2) receipt of immunotherapy (stage IV) using multivariable logistic regression. The association of insurance status with OS in metastatic patients who received immunotherapy was assessed using Kaplan-Meier and Cox proportional hazards analyses. The study included 167,130 patients; 52% had commercial insurance, 43% had Medicare, 3% had Medicaid and 2% were uninsured. In patients below 65 years, those with Medicaid and the uninsured had a higher likelihood of presenting with metastatic melanoma and were less likely to receive immunotherapy compared with those with commercial insurance. Further among those who received immunotherapy, patients with Medicaid (hazard ratio: 1.51, P=0.001) and no insurance (hazard ratio: 1.37, P=0.046) had an inferior OS. In patients 65 years or above, whereas Medicare was associated with an increased likelihood of presenting with metastatic disease, there was no significant difference in receipt of immunotherapy or OS as compared with commercial insurance. In this large modern cohort, insurance was associated with stage at diagnosis, receipt of immunotherapy, and OS for patients below 65 years old with melanoma.

12.
Laryngoscope ; 130(3): 691-697, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31411747

RESUMO

OBJECTIVE: In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS-assisted workup, we have adopted a pharyngeal-sparing radiation therapy (PSRT) approach targeting only the at-risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal-targeted RT (PRT). METHODS: Between 2009 and 2018, 172 patients underwent TORS-assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty-nine percent received PSRT and 51% received PRT. RESULTS: No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow-up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two-year RFS was 86% and 74% for PSRT and PRT patients, respectively (log-rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two-year OS for PSRT and PRT patients was 91% and 74%, respectively (log-rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment-related unplanned hospitalizations (9% vs. 39%, P = .04). CONCLUSION: Following TORS-assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure. LEVEL OF EVIDENCE: Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691-697, 2020.


Assuntos
Carcinoma/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Primárias Desconhecidas/radioterapia , Tratamentos com Preservação do Órgão/métodos , Doenças Faríngeas/prevenção & controle , Lesões por Radiação/prevenção & controle , Carcinoma/secundário , Carcinoma/cirurgia , Estudos de Casos e Controles , Feminino , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Pescoço/efeitos da radiação , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/cirurgia , Órgãos em Risco/patologia , Órgãos em Risco/efeitos da radiação , Doenças Faríngeas/etiologia , Faringe/patologia , Faringe/efeitos da radiação , Período Pós-Operatório , Lesões por Radiação/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
13.
Br J Radiol ; 92(1104): 20190466, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600090

RESUMO

OBJECTIVE: One approach to reduce treatment-related morbidity for human papilloma virus (HPV)-associated tonsil cancer is omitting radiotherapy to the contralateral neck. Pathologic risk factors for early contralateral neck disease, however, are poorly understood. We report on the risk contralateral neck failures from the time of pre-operative diagnostic imaging to time of planning for adjuvant radiation in a single institution series of HPV-associated tonsillar cancer patients undergoing surgery followed by radiotherapy (RT). METHODS: Retrospective analysis of 123 patients with T1-T3 HPV-positive tonsillar squamous cell carcinoma treated between 2010 and 2016 with transoral robotic surgery and selective ipsilateral neck dissection followed by adjuvant RT. Contralateral neck recurrence was classified as the detection of a pathologic node in the contralateral neck prior to initiation of adjuvant RT. RESULTS: Seven patients (5.7%) developed contralateral neck disease/failure between the time of pre-operative diagnostic neck imaging and time of planning of adjuvant radiation. Increased ratio of positive/resected nodes [odds ratio (OR) 1.073, p = 0.005] was significantly associated with increased risk of contralateral neck recurrence, with a trend found for close/positive margins (OR 5.355, p = 0.06), tumor size (OR 2.046, p = 0.09), and total number of nodes positive (OR 1.179, p = 0.062). CONCLUSIONS: Patients who develop very early contralateral neck disease, between completion of ipsilateral neck dissection and the initiation of radiotherapy, have a higher ratio of positive nodes to total nodes resected in the ipsilateral neck. These findings suggest that proper selection of patients for omission of treatment of the contralateral, node-negative neck should be made with this in mind, with future studies needed to document the impact on toxicity and disease outcomes from such an approach. ADVANCES IN KNOWLEDGE: Pathologic risk factors in the dissected, ipsilateral neck in patients with tonsil cancer may inform the risk of contralateral neck failure. Patient selection for future, prospective efforts to examine sparing of the contralateral neck need to be based with these risk factors in mind.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Segunda Neoplasia Primária/etiologia , Infecções por Papillomavirus/complicações , Neoplasias Tonsilares/radioterapia , Neoplasias Tonsilares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Razão de Chances , Papillomaviridae , Período Pós-Operatório , Radioterapia Adjuvante/métodos , Radioterapia de Intensidade Modulada , Análise de Regressão , Estudos Retrospectivos , Risco , Neoplasias Tonsilares/patologia , Neoplasias Tonsilares/virologia , Carga Tumoral
14.
Head Neck ; 41(11): 3858-3868, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31411356

RESUMO

BACKGROUND: For patients with head and neck squamous cell carcinoma (SCC) undergoing surgery followed by postoperative radiotherapy (PORT), time from surgery to completion of adjuvant therapy, "package time" impacts locoregional control (LRC). However, the significance of package time in HPV+ oropharyngeal SCC (OPSCC) is unknown. METHODS: We examined patients undergoing TORS resection with PORT for HPV+ OPSCC from January 2010 to December 2015 with ≥18 months follow-up (n = 267). A cutoff of 15 weeks was used to delineate patients into short and long package time groups. LRC loss was defined as any recurrence after surgery. RESULTS: Prolonged package time >15 weeks was associated with inferior LRC in this HPV+ OPSCC cohort, driven primarily by interval from surgery to PORT initiation. Multivariate analysis showed that package time and T classification are both independently associated with LRC. CONCLUSIONS: Among HPV+ OPSCC, prolongation of package time appears to compromise LRC, but not survival.


Assuntos
Carcinoma de Células Escamosas/terapia , Duração da Terapia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento
15.
Int J Radiat Oncol Biol Phys ; 104(3): 553-562, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625409

RESUMO

PURPOSE: The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) for oropharynx cancer and to use a model-based approach to investigate the added value of PBT in preventing treatment complications. METHODS AND MATERIALS: For patients with advanced-stage oropharynx cancer treated with curative intent (PBT, n = 30; IMRT, n = 175), NTCP models were developed using multivariable logistic regression analysis with backward selection. For PBT-treated patients, an equivalent IMRT plan was generated to serve as a reference to determine the benefit of PBT in terms of NTCP. The models were then applied to the PBT-treated patients to compare predicted and observed clinical outcomes (calibration-in-the-large). Five binary endpoints were analyzed at 6 months after treatment: dysphagia ≥ grade 2, dysphagia ≥ grade 3, xerostomia ≥ grade 2, salivary duct inflammation ≥ grade 2, and feeding tube dependence. Corresponding toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Paired t tests and Wilcoxon rank tests were used to compare mean NTCP results for endpoints between PBT and IMRT. RESULTS: NTCP models developed based on outcomes from all patients were applied to those receiving PBT. NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing significantly higher NTCP values with IMRT. PBT was associated with statistically significant reductions in the mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of ≥grade 2 dysphagia and ≥grade 2 xerostomia. CONCLUSIONS: NTCP models predict significant improvements in the probability of short-term, treatment-related toxicity with PBT compared with IMRT for oropharyngeal cancer. This study demonstrates an NTCP model-based approach to compare predicted patient outcomes when randomized data are not available.


Assuntos
Órgãos em Risco/efeitos da radiação , Neoplasias Orofaríngeas/radioterapia , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Transtornos de Deglutição/classificação , Transtornos de Deglutição/etiologia , Nutrição Enteral/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Tratamentos com Preservação do Órgão , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Probabilidade , Terapia com Prótons/efeitos adversos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada/efeitos adversos , Análise de Regressão , Sialadenite/etiologia , Xerostomia/classificação , Xerostomia/etiologia
16.
Br J Cancer ; 119(10): 1200-1207, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30318516

RESUMO

BACKGROUND: We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers. METHODS: There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) and the other(s) followed for response. RESULTS: Of the 24 patients, 20 (83%) had treatment-related adverse events (AEs) (all grade 1 or 2). There were eight grade 3 AEs, none treatment related. There were no dose-limiting toxicities or grade 4/5 AEs. Stratum 1: two patients (of 12) with progression on prior PD-1 blockade experienced prolonged responses (9.2 and 28.1 months). Stratum 2: one patient experienced a complete response and two had prolonged stable disease (7.4 and 7.0 months). Immune profiling demonstrated that anti-PD-1 therapy and radiation induced a consistent increase in the proliferation marker Ki67 in PD-1-expressing CD8 T cells. CONCLUSIONS: HFRT was well tolerated with pembrolizumab, and in some patients with metastatic NSCLC or melanoma, it reinvigorated a systemic response despite previous progression on anti-PD-1 therapy. CLINICAL TRIAL REGISTRATION: NCT02303990 ( www.clinicaltrials.gov ).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Hipofracionamento da Dose de Radiação , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/radioterapia , Neoplasias Cutâneas/patologia
17.
Am J Clin Oncol ; 41(11): 1118-1124, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29553972

RESUMO

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is potentially curative treatment for small hepatocellular carcinomas (HCC), but data are limited on its efficacy and toxicity. We hypothesized that SBRT can achieve excellent local control (LC) with acceptable toxicity treating HCC lesions, even in advanced cirrhosis. MATERIALS AND METHODS: Thirty-seven nonmetastatic HCC patients received SBRT to 43 lesions between October 2012 and April 2016. Median dose was 50 Gy/5 fractions. All Child-Pugh (CP) ≥B patients underwent a planned 1-month break after the first 3 fractions to assess hepatic toxicity. Patients were treated without separately placed fiducial markers using Linac-based SBRT with breath-hold (67%) or 4D-computed tomography with compression belt (33%) to reduce motion. Patients underwent magnetic resonance imaging q3 months post-SBRT. RESULTS: Median age was 65 (range, 44 to 88). Pre-SBRT mean CP was 6.4 (range, A5 to C11). Nine (24%) had CP≥B8. Thirty-one of 33 patients (93%) had prior liver-directed therapy (median 2). Seventeen (40%) had solitary lesions. Median lesion diameter was 2.7 cm (range, 1.1 to 5.6). Median follow-up was 14 months (range, 2 to 45). There was 1 local failure (multifocal HCC with 3 prior transarterial chemoembolization). LC, freedom from liver progression, and overall survival at 12 months was 95%, 66%, 87% in the full cohort, and 100%, 76%, 93% for patients with solitary lesions. Four had grade 3 toxicity (ascites [n=2]/gastrointestinal bleed [n=1]/capsular pain [n=1]). Eight of 9 CP≥B8 patients had no grade ≥3 hepatic toxicity. CONCLUSIONS: SBRT for HCC is well-tolerated even in patients with advanced cirrhosis and prior liver-directed treatment and provides excellent LC even for larger lesions that cannot be controlled with radiofrequency ablation. LC with SBRT compares favorably to other liver-directed therapies. Prospective studies comparing SBRT with other liver-directed therapies are warranted.

18.
Head Neck ; 40(6): 1147-1155, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29394465

RESUMO

BACKGROUND: The purpose of this study was to determine national disparities in head and neck cancer treatment package time (the time interval from surgery through the completion of radiation) and the associated impact on survival. METHODS: We conducted an observational cohort study using the National Cancer Database of 15 234 patients with resected head and neck cancer who underwent adjuvant radiotherapy from 2004-2012. Predictors of prolonged package time were identified by multivariable linear regression. Survival outcomes were assessed using a multivariable Cox model. RESULTS: Mean package time was 100 days (SD 23). Package time was 7.52 days (95% confidence interval [CI] 6.23-8.81; P < .001) longer with Medicaid versus commercial insurance. Low income and African American race also predicted for longer package times. All-cause mortality increased an average of 4% with each 1 week increase in treatment package time (hazard ratio [HR] 1.04; 95% CI 1.03-1.05; P < .001). CONCLUSION: Significant national socioeconomic disparities exist in treatment package time. Treatment delays in this setting may contribute to worse survival outcomes.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Afro-Americanos/estatística & dados numéricos , Idoso , Quimiorradioterapia , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Disparidades em Assistência à Saúde/etnologia , Humanos , Modelos Lineares , Masculino , Medicaid , Pessoa de Meia-Idade , Pobreza/etnologia , Pobreza/estatística & dados numéricos , Taxa de Sobrevida , Tempo para o Tratamento/estatística & dados numéricos , Estados Unidos/epidemiologia
19.
Cancer Chemother Pharmacol ; 81(3): 609-614, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29362902

RESUMO

PURPOSE: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma. METHODS: We performed a phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n = 3) or 125 mg/m2 (n = 6). There were no observed grade 3 gastrointestinal toxicities. One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%) and neutropenia (11%). No grade 4 toxicities were observed. Following chemoradiotherapy, four patients (borderline resectable, n = 2 and unresectable, n = 2) underwent surgical resection, all with negative margins and with significant treatment effect with limited tumor viability. CONCLUSIONS: The combination of fractionated radiation and weekly full dose nab-paclitaxel was safe and well-tolerated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/terapia , Idoso , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/métodos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Diarreia/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do Tratamento
20.
Cureus ; 10(11): e3648, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30723647

RESUMO

Purpose A new dual-layer multi-leaf collimator (MLC) system with several improved characteristics was introduced with the Varian Halcyon™ treatment platform. This study evaluated this new MLC's impact on head and neck plan quality and delivery efficiency. Methods Nine patients were retrospectively studied with Institutional Review Board (IRB) approval. To compare plan quality between the Halcyon dual-layer MLC and Truebeam® MLC, all patients were replanned with the same prescription and target coverage following the institutional clinical protocol for both platforms and using both intensity modulated radiation therapy (IMRT) or volumetrically modulated arc therapy (VMAT) techniques. Organs-at-risk (OAR) dose-volume histogram (DVH) statistics were compared along with total plan monitor units (MU). To evaluate delivery efficiency, actual beam-on time for five patients' plans were recorded and compared. To evaluate the impact of MLC performance parameters on plan quality, virtual MLC models were generated by matching Truebeam MLC's parameters to those of the Halcyon dual-layer MLC both individually and combined. OAR doses were then compared between these virtual MLCs, the Truebeam MLC, and the actual Halcyon MLC. Results Overall the Halcyon dual-layer MLC provided similar plan quality compared to Truebeam MLC for VMAT plans, and improved sparing for majority of the OARs when using IMRT. Paired comparison showed median dose differences in mean doses to the parotids, cochlea, esophagus, and larynx ranged from -0.83 Gy to 0.37 Gy for VMAT, and from -4.79 Gy to -0.04 Gy for IMRT, with negative values indicating improved performance by Halcyon. Despite a slight increase in plan MU, the Halcyon reduced the total beam-on time by 42.8 ± 8.5%. Virtual MLC simulations demonstrated that matching MLC transmission accounted for nearly half of the total dose difference between Halcyon and Truebeam IMRT plans. Conclusion When compared to the Truebeam, the Halcyon's dual-layer MLC achieved similar plan quality using VMAT, and improved OAR sparing using IMRT, while providing nearly twice as fast treatment delivery. Reduction in MLC transmission is the dominating factor contributing to dosimetric differences in OAR sparing.

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