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Objectives: A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients. Methods: Retrospective cohort study using Veterans Affairs (VA) database. T1-T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan-Meier analyses were implemented. Results: Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96-0.98]; p < .001) and N3 disease (0.42 [0.18-1.00]; p = .050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04-1.43]; p = .015) and >T1 disease (T2, 1.76 [1.44-2.17]; p < .001; T3, 2.06 [1.58-2.68]; p < .001; T4, 1.79 [1.26-2.53]; p = .001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10-1.55]; p = .003) and N3 (2.02 [1.25-3.26]; p = .004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70-0.99]; p = .044). Those who do not receive TL following local recurrence have poorer disease-specific survival (log-rank, p < .001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83-9.82]; p < .001). Conclusion: Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence. Level of Evidence: Level 3.
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Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes. Methods: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis. Results: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes. Conclusions: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Tolerância a Radiação , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Hipóxia Tumoral/efeitos da radiação , Radiossensibilizantes/uso terapêutico , Hipóxia CelularRESUMO
Purpose/Objectives: We sought to create nomograms to predict individual risk of early mortality, which can identify patients who require interventions to prevent early death. Methods: We included patients in the National Cancer Database with non-metastatic squamous cell carcinoma of the head and neck who received radiation and systemic therapy between 2004 and 2017 in the definitive or adjuvant setting. Early mortality was defined as any death less than 90 days after starting radiation. Multivariable logistic regression was used to assess the relationship between covariates and early mortality. Nomograms to predict the risk of early death were created for both the definitive and adjuvant settings. Results: Among 84,563 patients in the definitive group and 18,514 patients in the adjuvant group, rates of early mortality were 3.5 % (95 % CI 3.4-3.7 %) and 2.2 %, (95 % CI 1.9-2.4 %), respectively. Patients above the age of 70 had an early mortality rate of 7.8 % (95 % CI 7.3-8.2 %) in the definitive group and 4.4 % (95 % CI 3.6-5.4 %) in the adjuvant group. In the multivariable analysis, age, comorbidity, T and N category, and tumor site were associated with early mortality in both cohorts (p < 0.05 for all). Nomograms including age, comorbidity, T and N category and tumor site performed better than age alone at predicting early mortality (AUC for definitive group: 0.70 vs 0.66; AUC for adjuvant group: 0.71 vs 0.61). Conclusion: Nomograms including age, comorbidity, T and N category and tumor site were developed to predict the risk of early death following definitive or adjuvant chemoradiation.
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BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. INTERVENTION: Short-term ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score. RESULTS AND LIMITATIONS: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards. CONCLUSIONS: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT. PATIENT SUMMARY: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.
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Antagonistas de Androgênios , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Seguimentos , Antígeno Prostático Específico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: In select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA-sequencing (RNA-seq) expression is a robust method for predicting overall survival (OS) and distant metastasis-free survival (DMFS) in patients with resected pancreatic adenocarcinoma. METHODS: Utilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I-III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA-seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA-seq via multivariable models and receiver operator characteristic curves. RESULTS: In TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00-2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87-2.03; p = .19). Low SMAD4 RNA-seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17-2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14-2.54; p = .009). In the ICGC, increased SMAD4 RNA-seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86-.94) and DMFS (AUC, .84; 95% CI, .82-.87). CONCLUSIONS: In patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA-seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA-seq expression may be a useful marker to predict metastatic spread.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Proteína Smad4/genética , Modelos de Riscos Proporcionais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , PrognósticoRESUMO
There are over 220 identified genotypes of Human papillomavirus (HPV), and the HPV genome encodes 3 major oncogenes, E5, E6, and E7. Conservation and divergence in protein sequence and function between low-risk versus high-risk oncogenic HPV genotypes has not been fully characterized. Here, we used modern computational and structural folding algorithms to perform a comparative analysis of HPV E5, E6, and E7 between multiple low risk and high risk genotypes. We first identified significantly greater sequence divergence in E5 between low- and high-risk genotypes compared to E6 and E7. Next, we used AlphaFold to model the structure of papillomavirus proteins and complexes with high confidence, including some with no established consensus structure. We observed that HPV E5, but not E6 or E7, had a dramatically different 3D structure between low-risk and high-risk genotypes. To our knowledge, this is the first comparative analysis of HPV proteins using Alphafold artificial intelligence (AI) system. The marked differences in E5 sequence and structure in high-risk HPVs may contribute in important and underappreciated ways to the development of HPV-associated cancers.
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Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Papillomavirus Humano , Inteligência Artificial , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Papillomaviridae/genética , GenótipoRESUMO
Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and often fatal. This has prompted new efforts to intensify treatment in these patients with the addition of neoadjuvant or adjuvant immune checkpoint inhibitor therapy. However, newer diagnostic techniques have led to stage migration in patients with previously subclinical metastatic disease; consequently, preventing locoregional recurrence may be a higher priority in node-positive MCC patients than was previously believed. Recent trials in node-positive MCC, such as ADMEC-O, have had lower rates of adjuvant RT utilization in treatment versus control arms, which may have attenuated the observed effect of adjuvant immunotherapy. The low utilization of adjuvant RT may have also resulted in a higher recurrence rate in patients who did not have a complete response to neoadjuvant immunotherapy in the CHECKMATE 358 trial. Altogether, these are important considerations for ongoing and future immunotherapy trials in MCC and may affect the interpretation of their results. Ongoing clinical trials may determine which patients are at low risk of recurrence when treated with immunotherapy and whether adjuvant RT could be omitted in select patients.
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Importance: Patients with locally advanced non-human papillomavirus (HPV) head and neck cancer (HNC) carry an unfavorable prognosis. Chemoradiotherapy (CRT) with cisplatin or anti-epidermal growth factor receptor (EGFR) antibody improves overall survival (OS) of patients with stage III to IV HNC, and preclinical data suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and ERBB2 (formerly HER2 or HER2/neu) inhibitor may be more effective than anti-EGFR antibody therapy in HNC. Objective: To examine whether adding lapatinib, a dual EGFR and HER2 inhibitor, to radiation plus cisplatin for frontline therapy of stage III to IV non-HPV HNC improves progression-free survival (PFS). Design, Setting, and Participants: This multicenter, phase 2, double-blind, placebo-controlled randomized clinical trial enrolled 142 patients with stage III to IV carcinoma of the oropharynx (p16 negative), larynx, and hypopharynx with a Zubrod performance status of 0 to 1 who met predefined blood chemistry criteria from October 18, 2012, to April 18, 2017 (median follow-up, 4.1 years). Data analysis was performed from December 1, 2020, to December 4, 2020. Intervention: Patients were randomized (1:1) to 70 Gy (6 weeks) plus 2 cycles of cisplatin (every 3 weeks) plus either 1500 mg per day of lapatinib (CRT plus lapatinib) or placebo (CRT plus placebo). Main Outcomes and Measures: The primary end point was PFS, with 69 events required. Progression-free survival rates between arms for all randomized patients were compared by 1-sided log-rank test. Secondary end points included OS. Results: Of the 142 patients enrolled, 127 (median [IQR] age, 58 [53-63] years; 98 [77.2%] male) were randomized; 63 to CRT plus lapatinib and 64 to CRT plus placebo. Final analysis did not suggest improvement in PFS (hazard ratio, 0.91; 95% CI, 0.56-1.46; P = .34) or OS (hazard ratio, 1.06; 95% CI, 0.61-1.86; P = .58) with the addition of lapatinib. There were no significant differences in grade 3 to 4 acute adverse event rates (83.3% [95% CI, 73.9%-92.8%] with CRT plus lapatinib vs 79.7% [95% CI, 69.4%-89.9%] with CRT plus placebo; P = .64) or late adverse event rates (44.4% [95% CI, 30.2%-57.8%] with CRT plus lapatinib vs 40.8% [95% CI, 27.1%-54.6%] with CRT plus placebo; P = .84). Conclusion and Relevance: In this randomized clinical trial, dual EGFR-ERBB2 inhibition with lapatinib did not appear to enhance the benefit of CRT. Although the results of this trial indicate that accrual to a non-HPV HNC-specific trial is feasible, new strategies must be investigated to improve the outcome for this population with a poor prognosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01711658.
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Carcinoma , Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Feminino , Cisplatino/efeitos adversos , Lapatinib , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma/tratamento farmacológico , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Importance: Spine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control. Objective: To assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases. Design, Setting, and Participants: In this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020. Interventions: Patients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below. Main Outcomes and Measures: The primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord. Results: A total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, -19 percentage points; 95% CI, -32.9 to -5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months. Conclusions and Relevance: In this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential. Trial Registration: ClinicalTrials.gov Identifier: NCT00922974.
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Fraturas por Compressão , Radiocirurgia , Fraturas da Coluna Vertebral , Humanos , Masculino , Adolescente , Feminino , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Fraturas da Coluna Vertebral/etiologia , Qualidade de Vida , Fraturas por Compressão/etiologia , Coluna Vertebral/cirurgia , Dor/etiologiaRESUMO
PURPOSE: To develop and test a method for fully automated segmentation of bony structures from whole-body computed tomography (CT) and evaluate its performance compared with manual segmentation. METHODS AND MATERIALS: We developed a workflow for automatic whole-body bone segmentation using atlas-based segmentation (ABS) method with a postprocessing module (ABSPP) in MIM MAESTRO software. Fifty-two CT scans comprised the training set to build the atlas library, and 29 CT scans comprised the test set. To validate the workflow, we compared Dice similarity coefficient (DSC), mean distance to agreement, and relative volume errors between ABSPP and ABS with no postprocessing (ABSNPP) with manual segmentation as the reference (gold standard). RESULTS: The ABSPP method resulted in significantly improved segmentation accuracy (DSC range, 0.85-0.98) compared with the ABSNPP method (DSC range, 0.55-0.87; P < .001). Mean distance to agreement results also indicated high agreement between ABSPP and manual reference delineations (range, 0.11-1.56 mm), which was significantly improved compared with ABSNPP (range, 1.00-2.34 mm) for the majority of tested bony structures. Relative volume errors were also significantly lower for ABSPP compared with ABSNPP for most bony structures. CONCLUSIONS: We developed a fully automated MIM workflow for bony structure segmentation from whole-body CT, which exhibited high accuracy compared with manual delineation. The integrated postprocessing module significantly improved workflow performance.
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Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
OPINION STATEMENT: Significant advancements have been made in the treatment of locally advanced head and neck cancer, predominantly driven by the integration of concurrent chemotherapy with radiation therapy as a standard of care for many patients. The most heavily investigated chemotherapeutic is cisplatin, yet many patients are ineligible for cisplatin due to the presence of pre-existing medical comorbidities. Moreover, given the toxicity profile of cisplatin, identifying which patients stand to benefit from cisplatin is challenging, which is particularly evident in older patients. Efforts to better risk-stratify patients based on age, performance status, and the degree of pre-existing comorbidities are ongoing and have been increasingly utilized in national clinical trials. In parallel, exploration into alternative systemic agents, including novel targeted therapies and immunotherapies, in cisplatin-ineligible patients are rapidly expanding. Cumulatively, identifying appropriate treatment paradigms in patients who harbor contraindications to cisplatin can not only improve clinical outcomes but also critically mitigate detrimental adverse effects.
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Antineoplásicos , Neoplasias de Cabeça e Pescoço , Humanos , Idoso , Cisplatino/uso terapêutico , Contraindicações , Imunoterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/efeitos adversosRESUMO
PURPOSE: To estimate local control, survival, and toxicity associated with a 3-fraction (3F) image-guided brachytherapy (IGBT) regimen compared to longer fraction (LF) for cervical cancer. METHODS: 150 patients treated between 2015-2020 with 3F (24Gy in 3 fractions) or LF (28...30 Gy in 4-5 fractions) were reviewed. The primary outcome was 2-year local failure. We compared overall survival (OS), disease-free survival (DFS), hospitalizations, and toxicity. RESULTS: There were 32 patients in the 3F group and 118 in the LF group, with a median follow up of 22 months. The 3F had worse performance status (p = 0.01) but otherwise similar characteristics. The 2-year local failure rate was 3.6% (95% CI 0%, 10.6%) for 3F, and 7.5% (95% CI 2.4%, 12.6%) for LF. The univariable hazard ratio (HR) for local failure for 3F was 0.43 (0.05, 3.43; p = 0.43). Moreover, 2 of 32 (6.3%) 3F patients experienced Grade ...3 toxicity compared to 7 of 118 (5.9%) LF patients (p = 1.0), with no difference in hospitalization within 2 years (p = 0.66) and no treatment-related deaths. CONCLUSIONS: Local control was excellent, with long term survival and toxicity similar between the groups. These findings support consideration of 3F.
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Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Intervalo Livre de Doença , Intervalo Livre de Progressão , Protocolos Clínicos , Dosagem RadioterapêuticaRESUMO
PURPOSE: To provide evidence-based recommendations for practicing physicians and other health care providers on immunotherapy and biomarker testing for head and neck cancers. METHODS: ASCO convened an Expert Panel of medical oncology, surgical oncology, radiation oncology, radiology, pathology, and patient advocacy experts to conduct a literature search, including systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2022. Outcomes of interest included survival, overall response, and locoregional control. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 28 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: When possible, evidence-based recommendations were developed to address biomarker testing, first-line treatment regimens based on programmed death ligand-1 scores, immunotherapy in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma, immunotherapy in nasopharyngeal carcinoma, and radiation therapy in combination with immunotherapy for treatment of local recurrence.Additional information is available at www.asco.org/head-neck-cancer-guidelines.
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Neoplasias de Cabeça e Pescoço , Humanos , Biomarcadores , Imunoterapia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown. METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms. RESULTS: Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol. CONCLUSIONS: Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593).
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Mucosite , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Nivolumabe/uso terapêutico , Cisplatino/uso terapêutico , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fadiga/tratamento farmacológicoRESUMO
OBJECTIVE: To determine characteristics most strongly associated with risk for aspiration events among head and neck cancer (HNC) patients undergoing curative intent treatment. MATERIALS AND METHODS: This was a retrospective, cross-sectional study of 106 patients with previously untreated HNC who received definitive or postoperative radiation therapy (RT) +/- systemic therapy with curative intent. Patients who received post-treatment videofluoroscopic swallow study (VFSS) between 2018-2021 were included. Using ordinal multivariable logistic regression, we modeled the effects of age (>60 years vs. ≤60 years), sex, body mass index (BMI) (>20 kg/m2 vs. ≤20 kg/m2), American Joint Committee on Cancer 8th edition stage (I-II vs. III-IVB), treatment with cisplatin (vs. other or no systemic therapy), post-operative status, primary site (oral cavity vs. P16+ oropharynx vs. P16- Mucosal Site vs. other), and quantitative VFSS measures on Penetration-Aspiration Scale (PAS) score. RESULTS AND CONCLUSION: On ordinal multivariable logistic regression, age >60 years (odds ratio (OR): 3.91, 95% confidence interval (CI): 1.29, 11.9), advanced stage (stage III-IVB) (OR: 3.13, 95% CI: 1.23, 7.79), pharyngeal constriction ratio (PCR) >0.25 (OR: 3.65, 95% CI: 1.14, 11.7), and bolus clearance ratio (BCR) > 0.10 (OR: 3.42, 95% CI: 1.20, 9.75) were found to be significant risk factors for higher PAS scores. Patients with ≥ 2 pre-treatment risk factors had statistically significant increased risk for post-treatment aspiration (OR 2.52, 95% CI: 1.31, 4.86) on ordinal logistic regression. This model could be useful to direct high-risk patients toward interventions designed to reduce risk of aspiration events.
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Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Humanos , Pessoa de Meia-Idade , Transtornos de Deglutição/etiologia , Estudos Retrospectivos , Estudos Transversais , Neoplasias de Cabeça e Pescoço/complicações , Modelos Logísticos , DeglutiçãoRESUMO
OBJECTIVE: To identify factors associated with receipt of incomplete cisplatin during chemoradiation for locally advanced cervical cancer and its impact on outcomes. METHODS: Patients with locally advanced cervical cancer treated with chemoradiation at our institution between November 2015 and August 2020 were retrospectively identified. Patients who received ≤4 cycles were identified as the 'incomplete' cohort and those who received 5-6 cycles as the 'complete' cohort. The primary endpoint of incomplete chemotherapy was evaluated with multivariable logistic regression. Secondary endpoints of locoregional failure, overall survival, and distant failure were evaluated in multivariable Cox and Fine-Gray models. RESULTS: Of 140 patients with locally advanced cervical cancer that underwent chemoradiation, 22 (15.7%) received an incomplete cisplatin regimen (8 with 0 cycles, 14 with 1-4 cycles). The most common reasons for receiving incomplete treatment were comorbidities/infections (41%), unmet laboratory parameters (27%), and cisplatin intolerance (14%). In multivariable models, only poor (2-4) Eastern Cooperative Oncology Group performance status was a significant predictor as these patients were 41 times more likely to receive incomplete chemotherapy (odds ratio (OR), 95% confidence interval (CI) 4.57 to 375.15, p<0.001). Median follow-up time was 20 months (range 4-64). In multivariable models, receipt of incomplete cisplatin was significantly associated with higher recurrence (locoregional failure hazard ratio (HR) 3.02, 95% CI 1.08 to 8.45, p=0.03; distant failure HR 2.71, 95% CI 1.13 to 6.47, p=0.02) and worse survival (overall survival HR 4.91, 95% CI 1.27 to 18.98, p=0.02). CONCLUSION: Incomplete cisplatin regimen was associated with worse oncologic outcomes. Poor performance status was the only factor associated with receiving an incomplete regimen. This notable proportion of patients may be a target for better tolerated novel targeted anticancer agents in order to improve outcomes.