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Cancer is a disease of aging and is rapidly becoming the number one cause of mortality in older people. Over their lifetime, one in two men and one in three women will develop a cancer, with half of the risk being beyond the age of seventy. Therefore, cancer is a problem frequently encountered by geriatricians. In this article, we review a few recent progresses that will be of interest to the geriatric community. First, we now have robust evidence that a comprehensive geriatric assessment and management change outcomes in older cancer patients, notably allowing decreased treatment toxicity, better treatment completion, and increased functional outcomes. In gastrointestinal cancers and breast cancer, several recent studies have addressed when treatment intensity can be decreased, and when it cannot. New treatments for acute myeloid leukemia are finally beginning to improve outcomes for older patients and such patients should be referred to oncologists for management. In prostate cancer, new imaging techniques (e.g., PSMA scan) and treatment options can allow better treatment targeting and spare some hormonal and chemotherapy toxicity. Finally, we review recent public policy efforts to address the epidemiologic wave of cancer in older patients on a global scale.
Subject(s)
Breast Neoplasms , Male , Aged , Humans , Female , Geriatric Assessment/methods , AgingABSTRACT
BACKGROUND: Data about patient-reported outcomes (PROs) among patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors are sparse. Our exploratory study evaluated PROs in patients with HNSCC starting treatment with immune checkpoint inhibitor monotherapy or combination therapy with cetuximab. METHODS: Patients were recruited prior to receipt of their first checkpoint inhibitor therapy infusion. Participants completed measures of checkpoint inhibitor toxicities and quality of life (QOL) at on-treatment clinic visits. RESULTS: Among patients treated with checkpoint inhibitor monotherapy (n = 48) or combination therapy (n = 38) toxicity increased over time (p < 0.05), while overall QOL improved from baseline to 12 weeks, with stable or declining QOL thereafter (p < 0.05). There were no group differences in change in toxicity index or QOL. Toxicity index scores were significantly higher in the combination group at 18-20 weeks and 6 months post-initiation of immune checkpoint inhibitor (p < 0.05). There were no significant group differences at baseline, the 6-8 week (p = 0.13) or 3-month (p = 0.09) evaluations. The combination group reported better emotional well-being at baseline than the monotherapy group (p = 0.04), There were no other group differences QOL at baseline or later timepoints. CONCLUSIONS: Despite increasing patient-reported toxicity, checkpoint inhibitor monotherapy and combination therapy were associated with similar transient improvements, then worsening, of QOL in patients with HNSCC.
Subject(s)
Head and Neck Neoplasms , Quality of Life , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/etiology , Immune Checkpoint Inhibitors , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/etiology , Immunotherapy/adverse effects , Patient Reported Outcome MeasuresABSTRACT
PURPOSE: Patients with locoregional recurrence of squamous cell carcinoma of the head and neck (SCCHN) have relatively poor outcomes; therefore, stereotactic body radiation therapy (SBRT) has been investigated for this patient population. We performed a phase 1 clinical trial to establish a maximum tolerated dose of SBRT with concurrent cisplatin in previously irradiated locoregional SCCHN. METHODS AND MATERIALS: Patients with recurrent SCCHN who had previously undergone radiation therapy to doses ≥45 Gy to the area of recurrence ≥6 months before enrollment and who were not surgical candidates or refused surgery were eligible. SBRT was delivered every other day for 5 fractions. Starting dose level was 6 Gy × 5 fractions, followed by 7 Gy × 5 fractions and 8 Gy × 5 fractions. Chemotherapy consisted of cisplatin given before every SBRT fraction at a dose of 15 mg/m2. Patients were monitored for dose-limiting toxicities (DLT) that occurred within 3 months from the start of SBRT. Secondary endpoints included locoregional failure, distant metastasis, and overall survival. RESULTS: Twenty patients were enrolled, with 18 patients evaluable for endpoints. One patient at dose level 1 (30 Gy) died of unknown causes 2 weeks following completion of treatment. Therefore, an additional 3 patients were accrued to the 30-Gy dose level, with no further DLTs observed. Three patients were then accrued at dose level 2 (35 Gy) and 9 patients at dose level 3 (40 Gy) without DLTs. At a median follow-up of 9.5 months, cumulative incidence of locoregional failure at 2 years was 61% (95% confidence interval [CI], 12%-66%), cumulative incidence of distant metastasis was 11% (95% CI, 74%-100%) at 2 years, and overall survival was 22% (95% CI, 9%-53%) at 2 years. CONCLUSIONS: Concurrent cisplatin and reirradiation with an SBRT dose of ≤40 Gy was safe and feasible in patients with locoregionally recurrent or second primary SCCHN.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Radiosurgery , Re-Irradiation , Humans , Cisplatin , Squamous Cell Carcinoma of Head and Neck/therapy , Radiosurgery/adverse effects , Radiosurgery/methods , Re-Irradiation/adverse effects , Head and Neck Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
PURPOSE: A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with a combination of cetuximab and nivolumab. PATIENTS AND METHODS: Patients with R/M HNSCC were treated with cetuximab 500 mg/m2 i.v. on day 14 as a lead-in followed by cetuximab 500 mg/m2 i.v. and nivolumab 240 mg i.v. on day 1 and day 15 of each 28-day cycle. Expression of p16 and programmed cell death-ligand 1 (PD-L1) in archived tumors were determined. Tumor-tissue-modified human papillomavirus (TTMV) DNA was quantified in plasma. RESULTS: Ninety-five patients were enrolled, and 88 patients were evaluable for OS with a median follow-up of 15.9 months. Median OS in the 45 patients who had prior therapy for R/M HNSCC (cohort A) was 11.4 months, with a 1 year OS 50% [90% confidence interval (CI), 0.43-0.57]. Median OS in the 43 patients who had no prior therapy (cohort B) was 20.2 months, with a 1-year OS 66% (90% CI, 0.59-0.71). In the combined cohorts, the p16-negative immunostaining was associated with higher response rate (RR; P = 0.02) but did not impact survival while higher PD-L1 combined positive score was associated with higher RR (P = 0.03) and longer OS (log-rank P = 0.04). In the p16-positive patients, lower median (1,230 copies/mL) TTMV DNA counts were associated with higher RR (P = 0.01) and longer OS compared with higher median (log-rank P = 0.05). CONCLUSIONS: The combination of cetuximab and nivolumab is effective in patients with both previously treated and untreated R/M HNSCC and warrants further evaluation.
Subject(s)
Head and Neck Neoplasms , Nivolumab , B7-H1 Antigen/metabolism , Cetuximab , Head and Neck Neoplasms/drug therapy , Humans , Neoplasm Recurrence, Local/pathology , Squamous Cell Carcinoma of Head and Neck/drug therapyABSTRACT
Background Cluster of differentiation 26/dipeptidyl peptidase-4 (DPP4) is a cell surface glycoprotein with multifaceted roles, including immune regulation, glucose metabolism, and tumorigenesis. Recent literature has identified DPP4 inhibitors to improve survival in diabetic patients with prostate cancer. DPP4 inhibitors have been proposed to play a role in prostate cancer, as DPP4 is found at higher levels in malignant prostate tissue compared to benign and correlates with PSA levels and cancer stage. In this multi-center retrospective study, we aim to define the effects of DPP4 inhibitors on progression-free survival (PFS) in diabetic patients with advanced-stage prostate cancer. Methodology We performed a retrospective analysis of 161 patients with diabetes and advanced-stage (III or IV) prostate cancer at the University of Florida Health Cancer Center and Moffitt Cancer Center. Our cohort included 120 patients on metformin (control group) and 41 on a DPP4 inhibitor (study group). Results No significant difference in progression of prostate cancer was identified between those on DPP4 inhibitors versus metformin (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.64-1.61; p = 0.955). Median time to progression was 3.5 years (range: 2.4-4.6 years). Conclusions Despite prior literature indicating survival benefit of DPP4 inhibitors in prostate cancer, our study did not identify a statistically significant improvement of PFS in diabetic patients with advanced prostate cancer. Additional analysis with larger sample sizes and prospective investigation with study of tumor microenvironment are needed to evaluate clinical impact and potential survival benefit of DPP4 inhibitors in prostate cancer.
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We hypothesized the combination of cetuximab and nivolumab would improve survival in recurrent and/or metastatic (R/M) HNSCC by providing synergy in cancer control and evaluated toxicities and efficacy of the combination. Effects of sequential administration of cetuximab and anti-Programmed Cell Death-1 checkpoint inhibitors (CPI) were also explored. Patients who failed at least one line of palliative treatment for incurable HNSCC were treated with cetuximab 500 mg/m2 IV on Day (D)-14 as a lead-in followed by cetuximab 500 mg/m2 IV and nivolumab 240 mg/m2 IV on D1 and D15 every 28-D cycle. Electronic health record-derived real-world data (RWD) were used to explore sequential treatment effects of CPI and cetuximab. A total of 45 evaluable patients were analyzed, and 31/45 (69%) patients had prior exposure to either CPI or cetuximab. The only grade 4 treatment-related adverse event was cetuximab infusion reaction in one patient. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 19% and 44%, respectively. Although patients with no prior CPI (23/45, 51%) showed a trend for more favorable PFS relative to patients with prior CPI (22/45, 49%), the improvement in the 1-year OS did not reach the statistical threshold. For evaluation of sequential CPI and cetuximab treatment effects, we selected RWD-cetuximab cohort with 173 patients and RWD-CPI cohort with 658 patients from 6862 R/M HNSCC. Our result suggested patients treated with RWD-cetuximab after RWD-CPI had worse OS compared to no prior RWD-CPI (HR 1.81, 95% CI 1.02-3.16). Our data suggest the combination of cetuximab and nivolumab is well tolerated. Optimal sequencing of cetuximab and CPI may have an impact in prognosis and requires further evaluation.
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PURPOSE: To examine the role age plays in the treatment and prognosis of locally advanced head and neck cancer (LAHNC) treated definitively with radiation alone or combined modality therapy. METHODS: A retrospective analysis was performed of three NRG/RTOG trials examining either radiation alone or combined radiation and systemic therapy for LAHNC. The effect of age (≥70 yrs.) on cause-specific survival (CSS), overall survival (OS), and toxicity was evaluated. RESULTS: A total of 2688 patients were analyzed, of whom 309 patients (11.5%) were ≥ 70. For all studies combined, the hazard ratio (HR) for CSS for patients age ≥ 70 vs. those <70 was 1.33 (95%CI: 1.14-1.55, p < 0.001). For OS, the HR for patients age ≥ 70 vs. those <70 for all studies combined was 1.55 (95% CI 1.35-1.77, p < 0.001). After adjustment for all covariates, age ≥ 70 was associated with worse OS regardless of adjustment for smoking and p16 status. The survival difference was more pronounced in those receiving combined radiation and systemic therapy. Hematologic and renal toxicities were increased in combined modality trials in patients ≥70 years old. CONCLUSIONS: Patients age ≥ 70 with LAHNC were underrepresented in these clinical trials. Their CSS and OS proved inferior to patients <70 years old.
Subject(s)
Chemoradiotherapy , Head and Neck Neoplasms , Aged , Head and Neck Neoplasms/radiotherapy , Humans , Prognosis , Proportional Hazards Models , Retrospective StudiesABSTRACT
Transitions between hospital and community services and from child and adolescent to adult services have been identified as a priority for improvement in the child and adolescent mental health and addictions sector across Canada and internationally. Despite widespread recognition of the issue, there is very little in the way of evidence to guide policy and programming to improve transitions. Transition support workers have been identified as a promising intervention to facilitate successful transitions, and innovative programs involving transition workers are currently operating in the Canadian mental health sector. This commentary presents two case studies of existing transition worker programs in the Greater Toronto Area that link hospital and community mental health sectors for youth ages 12-18. We discuss program characteristics, the transition worker role, recommendations to organizations considering creating a similar service, and areas for future research. The goal of this commentary is to contribute to knowledge exchange and ultimately strengthen the evidence base for the transition worker role in child and adolescent mental health services.
Les transitions des services hospitaliers aux services communautaires, et des services pour enfants et adolescents aux services pour adultes ont été désignées comme étant une priorité pour améliorer le secteur de la santé mentale et des toxicomanies des enfants et des adolescents dans tout le Canada et sur la scène internationale. Malgré que cet enjeu soit largement reconnu, il y a très peu de données probantes pour guider les politiques et les programmes aptes à améliorer les transitions. Les travailleurs de soutien des transitions sont estimés constituer une intervention prometteuse pour faciliter des transitions réussies, et des programmes innovateurs qui emploient ces travailleurs de transition sont actuellement en activité dans le secteur canadien de la santé mentale. Ce commentaire présente deux études de cas de programmes de travailleurs de transition existants dans la région du Grand Toronto qui relient les secteurs hospitaliers et communautaires de la santé mentale pour les adolescents de 12 à 18 ans. Nous présentons les caractéristiques des programmes, le rôle des travailleurs de transition, les recommandations aux organisations qui envisagent de créer un service semblable, et les domaines de la future recherche. Ce commentaire vise à contribuer à l'échange de connaissances et finalement, à étoffer les données probantes concernant le rôle du travailleur de transition dans les services de santé mentale pour enfants et adolescents.
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BACKGROUND: Studies suggest treatment outcomes may vary between high (HVC)- and low-volume centers (LVC). Radiation therapy (RT) for head and neck cancer (HNC) requires weeks of treatment, the inconvenience of which may influence a patient's choice for treatment location. We hypothesized that receipt of RT for HNC at a HVC would influence outcomes compared to patients evaluated at a HVC, but who chose to receive RT at a LVC. METHODS: From 1998 to 2011, 1930 HNC patients were evaluated at a HVC and then treated with RT at either a HVC or LVC. Time-to-event outcomes and treatment factors were compared. RESULTS: Median follow-up was 34 months. RT was delivered at a HVC for 1368 (71%) patients and at a LVC in 562 (29%). Patients were more likely to choose HVC-RT if they resided in the HVC's county or required definitive RT (all P < 0.001). HVC-RT was associated with a significant improvement in 3-year LRC (84% vs 68%), DFS (68% vs 48%), and OS (72% vs 57%) (all P < 0.001). On multivariate analysis (MVA), HVC-RT independently predicted for improved LRC, DFS, and OS (all P < 0.05). CONCLUSIONS: In patients evaluated at a HVC, the choice of RT location was primarily influenced by their residing distance from the HVC. HVC-RT was associated with improvements in LRC, DFS, and OS in HNC. As treatment planning and delivery are technically demanding in HNC, the choice to undergo treatment at a HVC may result in more optimal delivered dose, RT duration, and outcome.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Adult , Aged , Aged, 80 and over , Female , Hospitals, High-Volume , Hospitals, Low-Volume , Humans , Male , Middle Aged , Patient Preference , Patient Selection , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: Big Data is widely seen as a major opportunity for progress in the practice of personalized medicine, attracting the attention from medical societies and presidential teams alike as it offers a unique opportunity to enlarge the base of evidence, especially for older patients underrepresented in clinical trials. This study prospectively assessed the real-time availability of clinical cases in the Health & Research Informatics Total Cancer Care™ (TCC) database matching community patients with cancer, and the impact of such a consultation on treatment. MATERIALS AND METHODS: Patients aged 70 and older seen at the Lynn Cancer Institute (LCI) with a documented malignancy were eligible. Geriatric screening information and the oncologist's pre-consultation treatment plan were sent to Moffitt. A search for similar patients was done in TCC and additional information retrieved from Electronic Medical Records. A report summarizing the data was sent and the utility of such a consultation was assessed per email after the treatment decision. RESULTS: Thirty one patients were included. The geriatric screening was positive in 87.1% (27) of them. The oncogeriatric consultation took on average 2.2 working days. It influenced treatment in 38.7% (12), and modified it in 19.4% (6). The consultation was perceived as "somewhat" to "very useful" in 83.9% (26). CONCLUSION: This study establishes a proof of concept of the feasibility of real time use of Big Data for clinical practice. The geriatric screening and the consultation report influenced treatment in 38.7% of cases and modified it in 19.4%, which compares very well with oncogeriatric literature. Additional steps are needed to render it financially and clinically viable.
Subject(s)
Big Data , Geriatric Assessment/methods , Medical Oncology/methods , Neoplasms/therapy , Aged , Aged, 80 and over , Female , Humans , Male , Outcome Assessment, Health Care/methods , Proof of Concept Study , Prospective StudiesABSTRACT
Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for > 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (> 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Nasopharyngeal Carcinoma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Nivolumab/therapeutic use , Adult , Aged , Biomarkers, Tumor/metabolism , Disease Progression , Female , HLA Antigens/metabolism , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Programmed Cell Death 1 Receptor/metabolism , Survival Rate , Treatment OutcomeABSTRACT
Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC-particularly those undergoing concurrent chemoradiation therapy-and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Geriatric Assessment , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Age Factors , Aged , Aged, 80 and over , Combined Modality Therapy , Comorbidity , Decision Support Techniques , Forecasting , Humans , Knowledge , Quality of Life , Radiotherapy , Squamous Cell Carcinoma of Head and NeckABSTRACT
PURPOSE: Concurrent chemoradiotherapy (CRT) is the standard of care for many sites of locally advanced head and neck squamous cell carcinomas (LAHNC). However, on meta-analysis, the addition of chemotherapy did not improve survival for patients >70years. We hypothesized that elderly patients treated with CRT would have increased toxicity without similar improvements in survival. METHODS: A single-institution, IRB-approved retrospective study took place from 2005 to 2012 including 369 patients treated with CRT for LAHNC. Multivariate models for death at 3months and death over time were developed using logistic regression and Cox modeling, respectively. RESULTS: Patients ≥70years were treated less often with concurrent cisplatin dosed every 3weeks (25.5% vs. 71.4%, respectively) and more often with weekly carboplatin (31.9% vs. 3.4%) than patients <70years (n=322; p<0.001). Patients ≥70years experienced increased toxicity during treatment with more frequently hospitalizations (36.2% vs. 21.1%; p=0.02) and a lower rate of PEG removal at last follow-up or death (77.1% vs. 92.9%; p=0.004). A higher proportion of patients ≥70years died within 3months (12.8% vs. 2.8%; p=0.001) following CRT. Patients ≥70 had an increased risk of death at 3months following CRT (odds ratio 5.19, 95% CI 1.64-16.41; p=0.005) and worse survival over time (hazard ratio 2.30, 95% CI 1.34-3.93; p=0.002). CONCLUSIONS: Patients ≥70years were more often treated with less toxic chemotherapy, yet experienced higher rates of hospitalization during treatment and increased rates of acute mortality following CRT. The efficacy of chemoradiotherapy for elderly patients should be evaluated in a prospective setting.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Radiotherapy, Intensity-Modulated/methods , Adult , Age Factors , Aged , Aged, 80 and over , Carboplatin/therapeutic use , Carcinoma, Squamous Cell/mortality , Cisplatin/therapeutic use , Deglutition Disorders , Female , Head and Neck Neoplasms/mortality , Hospitalization/statistics & numerical data , Humans , Logistic Models , Male , Middle Aged , Mortality , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival RateABSTRACT
BACKGROUND: Given the aggressive behavior of advanced salivary malignancies, the purpose of the current study was to explore the utility of adjuvant chemoradiotherapy (CRT) in this population. METHODS: A retrospective study of salivary carcinomas treated from 1998 to 2013 with postoperative CRT (37 patients) or radiotherapy (RT; 103 patients) was completed. RESULTS: The decision to utilize adjuvant CRT versus RT was influenced by tumor grade and histology, cervical lymph node status, surgical margins, and perineural invasion. In both treatment cohorts, high locoregional control rates were obtained (79% for CRT vs 91% for RT; p = .031). Multivariate Cox regression analysis did not identify a difference in 3-year progression-free survival (PFS) with the use of CRT versus RT (hazard ratio [HR] = 0.783; 95% confidence interval [CI] = 0.396-1.549; p = .482). CONCLUSION: Until prospective evidence is available, such as from Radiation Therapy Oncology Group 1008, the standard use of CRT for advanced salivary malignancies cannot be recommended. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.
Subject(s)
Chemoradiotherapy, Adjuvant , Radiotherapy, Adjuvant , Salivary Gland Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Salivary Gland Neoplasms/surgeryABSTRACT
BACKGROUND: Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management. METHODS: An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed. RESULTS: The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years. CONCLUSIONS: HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/diagnosis , Oropharyngeal Neoplasms/therapy , Papillomavirus Infections/complications , Radiation Injuries/diagnosis , Adult , Aged , Aged, 80 and over , Carboplatin/therapeutic use , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Cetuximab/therapeutic use , Chemoradiotherapy , Cisplatin/therapeutic use , Databases, Factual , Disease Management , Female , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/virology , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Oropharyngeal Neoplasms/complications , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Prognosis , Radiotherapy , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck , Survival RateABSTRACT
BACKGROUND: Cisplatin dosed every 3 weeks (CIS) or weekly cetuximab (CTX) concurrent with radiotherapy are standards of care for locally advanced head and neck squamous cell carcinoma (LAHNC). Retrospective comparisons of CIS and CTX have offered mixed conclusions. We compared outcomes between CIS and CTX in this patient population. METHODS: Between January 2006 and December 2011, we identified 279 patients who underwent definitive radiotherapy and concurrent systemic therapy for LAHNC. The median age difference between the CIS and CTX groups was relatively small (58 vs. 62 years, respectively) and CIS patients had a slightly higher rate of N2 disease than CTX patients (74% vs. 61%, respectively). RESULTS: Median follow-up was 27 months. Systemic therapy consisted of CIS in 241 (86.4%) and CTX in 38 (13.6%). Actuarial locoregional control of the CIS and CTX groups at 2 years were 91% and 90% (p=0.74), respectively. Actuarial 2 year distant metastasis rates between the groups were 8% and 12%, respectively (p=0.55), and actuarial 2 year overall survival between the groups were 87% and 89%, respectively (p=0.47). CONCLUSIONS: We found no difference in locoregional control, distant metastasis rate, or overall survival between patients treated with concurrent CIS or CTX.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/therapy , Cetuximab/administration & dosage , Cisplatin/administration & dosage , Head and Neck Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Despite resection followed by adjuvant radiotherapy, high-risk cutaneous squamous cell carcinomas of the head and neck region (SCCHN) often recur. Because adjuvant concurrent chemoradiation reduces recurrence among high-risk mucosal SCCHN, we sought to understand its efficacy among high-risk cutaneous SCCHN. METHODS: We conducted a retrospective cohort study of patients with cutaneous SCCHN who underwent adjuvant radiation or concurrent chemoradiation. Patients must have had stage III/IV with high-risk features, including metastatic involvement of ≥2 lymph nodes, positive margins, or extracapsular invasion. RESULTS: There were 61 patients: 27 (44%) received adjuvant radiation and 34 (56%) received adjuvant chemoradiation. The median recurrence-free survivals were 15.4 and 40.3 months, respectively. Adjuvant chemoradiation significantly decreased the risk of recurrence or death in a multivariable analysis: hazard ratio (HR) 0.31 (p = .01). However, a difference in overall survival was not found. CONCLUSION: For high-risk cutaneous SCCHN, adjuvant chemoradiation was associated with a better recurrence-free survival than adjuvant radiation alone.
Subject(s)
Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy, Adjuvant/methods , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Cohort Studies , Disease-Free Survival , Female , Head and Neck Neoplasms/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Postoperative Care/methods , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Skin Neoplasms/mortality , Squamous Cell Carcinoma of Head and Neck , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: Panobinostat, a histone deacetylase (HDAC) inhibitor, enhances antiproliferative activity in non-small cell lung cancer (NSCLC) cell lines when combined with erlotinib. We evaluated this combination in patients with advanced NSCLC and head and neck cancer. EXPERIMENTAL DESIGN: Eligible patients were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of twice weekly panobinostat plus daily erlotinib at four planned dose levels (DL). Pharmacokinetics, blood, fat pad biopsies (FPB) for histone acetylation, and paired pre and posttherapy tumor biopsies for checkpoint kinase 1 (CHK1) expression were assessed. RESULTS: Of 42 enrolled patients, 33 were evaluable for efficacy. Dose-limiting toxicities were prolonged-QTc and nausea at DL3. Adverse events included fatigue and nausea (grades 1-3), and rash and anorexia (grades 1-2). Disease control rates were 54% for NSCLC (n = 26) and 43% for head and neck cancer (n = 7). Of 7 patients with NSCLC with EGF receptor (EGFR) mutations, 3 had partial response, 3 had stable disease, and 1 progressed. For EGFR-mutant versus EGFR wild-type patients, progression-free survival (PFS) was 4.7 versus 1.9 months (P = 0.43) and overall survival was 41 (estimated) versus 5.2 months (P = 0.39). Erlotinib pharmacokinetics was not significantly affected. Correlative studies confirmed panobinostat's pharmacodynamic effect in blood, FPB, and tumor samples. Low CHK1 expression levels correlated with PFS (P = 0.006) and response (P = 0.02). CONCLUSIONS: We determined MTD at 30 mg (panobinostat) and 100 mg (erlotinib). Further studies are needed to further explore the benefits of HDAC inhibitors in patients with EGFR-mutant NSCLC, investigate FPB as a potential surrogate source for biomarker investigations, and validate CHK1's predictive role.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Head and Neck Neoplasms/drug therapy , Hydroxamic Acids/administration & dosage , Indoles/administration & dosage , Lung Neoplasms/drug therapy , Quinazolines/administration & dosage , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/mortality , Disease-Free Survival , Erlotinib Hydrochloride , Female , Head and Neck Neoplasms/mortality , Histone Deacetylase Inhibitors/administration & dosage , Histone Deacetylase Inhibitors/adverse effects , Humans , Hydroxamic Acids/adverse effects , Hydroxamic Acids/pharmacokinetics , Indoles/adverse effects , Indoles/pharmacokinetics , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Male , Maximum Tolerated Dose , Middle Aged , Panobinostat , Quinazolines/adverse effects , Quinazolines/pharmacokinetics , Treatment OutcomeABSTRACT
IMPORTANCE: Patients with oropharyngeal squamous cell carcinoma undergoing chemoradiotherapy may require percutaneous endoscopic gastrostomy (PEG) tube placement because of dehydration or significant weight loss. OBJECTIVES: To determine the need for the reactive placement of a PEG tube during chemoradiotherapy for oropharyngeal cancer and to identify patient or tumor factors associated with reactively requiring the placement of a PEG tube. DESIGN, SETTING, AND PARTICIPANTS: Single-institution retrospective review of 297 patients treated with intensity-modulated radiation therapy and concurrent chemotherapy for oropharyngeal squamous cell carcinoma between May 1, 2004, and June 30, 2012, with a minimum follow-up period of 3 months. EXPOSURE: Placement of a PEG tube. MAIN OUTCOMES AND MEASURES: Logistic regression analysis was used to identify independent risk factors associated with symptomatic requirement for the reactive placement of a PEG tube. RESULTS: In total, 128 patients did not receive a prophylactic PEG tube within 10 days of initiation of chemoradiotherapy. Fifteen of 128 patients (11.7%) required the reactive placement of a PEG tube during or within 3 months of chemoradiotherapy. The median time to PEG tube removal was 3.3 months, and 14 of 15 patients had their PEG tube removed at the last follow-up analysis. Independent risk factors for PEG tube placement included the following: accelerated irradiation fractionation (odds ratio, 4.3; 95% CI, 1.1-16.5; P = .04), a tumor T classification of 3 or higher (odds ratio, 3.5; 95% CI, 1.0-11.9; P = .04), a cumulative cisplatin dose of 200 mg/m² or higher (odds ratio, 6.7; 95% CI, 1.2-36.7; P = .03), and a body mass index (calculated as weight in kilograms divided by height in meters squared) of less than 25 (odds ratio, 5.8; 95% CI, 1.4-23.9; P = .02). CONCLUSIONS AND RELEVANCE: Although the overall risk is low, a body mass index of less than 25, accelerated irradiation fractionation, a tumor T classification of 3 or higher, and a cumulative cisplatin dose of 200 mg/m² or higher are associated with symptomatic need for the reactive placement of a PEG tube in patients with oropharyngeal cancer.
Subject(s)
Carcinoma, Squamous Cell/therapy , Deglutition Disorders/prevention & control , Endoscopy, Gastrointestinal/methods , Enteral Nutrition/instrumentation , Gastrostomy/methods , Oropharyngeal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Deglutition Disorders/epidemiology , Female , Florida/epidemiology , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Over the past decade, intensity-modulated radiation therapy (IMRT) has gained widespread use in the treatment of head and neck cancer. METHODS: All patients with squamous cell carcinoma of the oropharynx treated with primary IMRT with or without chemotherapy over a 5-year period were reviewed. Outcomes and morbidity were analyzed and compared with previously published data. RESULTS: In all, 170 patients were included in the analysis. The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 92%, 91%, 80%, and 87%, respectively. Feeding tubes were present in 55% of patients during treatment, but remained in only 1% 2 years following treatment. CONCLUSIONS: This study confirms that IMRT yields excellent treatment outcomes for oropharyngeal carcinoma. Although acute toxicity remains a problem, late toxicity rates are low and long-term feeding tube dependence is rare compared with conventional radiation therapy.