[Show abstract][Hide abstract] ABSTRACT: Black patients with head and neck cancer (HNC) have poorer survival and disease control compared to non-black patients, but disparities in death from non-cancer causes (i.e., competing mortality) are less well-studied.
We conducted an analysis of 538 patients (169 black, 369 non-black) with stage III-IV HNC treated on one of six multi-institutional protocols between 1993 and 2004 involving multi-agent chemoradiotherapy with or without surgery. Competing mortality was defined as death due to intercurrent comorbid disease, treatment-related morbidity, or unknown cause in the absence of disease recurrence, progression, or second malignancy. Cox proportional hazards and competing risks regression were used to estimate the effect of black race on competing mortality.
Black race was associated with increased rates of comorbidity, smoking, heavy alcohol use, advanced tumor stage, and poorer performance status (p<.001 for all). Compared to non-black patients, black HNC patients had a higher 5year cumulative incidence of disease progression (31.4%; 95% CI, 24.4-38.5% vs 23.4%; 95% CI, 19.1-28.1%) and competing mortality (28.1%; 95% CI, 21.2-35.3% vs 14.5%; 95% CI, 11.0-18.5%). When adjusting for age, male sex, body mass index, distance traveled, smoking and alcohol use, performance status, comorbidity, and tumor stage, the black race was associated with death from comorbid disease (Cox hazard ratio 2.13; 95% CI, 1.06-4.28, p=0.033).
Black patients with advanced HNC are at increased risk of both disease progression and death from competing non-cancer mortality, particularly death from comorbid disease. Improved strategies to manage comorbid disease may increase the benefit of treatment intensification in black patients.
[Show abstract][Hide abstract] ABSTRACT: Objectives
Chemoradiation therapy (CRT) remains a potentially curative treatment in patients with locally advanced head/neck cancer (LA-HNC). However, survival and other outcomes in older patients with head/neck cancer receiving chemoradiotherapy are not well established. This study was performed to elucidate selected outcomes in this patient population.
Materials and Methods
Retrospective study of LA-HNC patients ≥ 70 years of age who had received 5-fluorouracil-hydoxyurea-based CRT with a minimum of 3 years of follow up after therapy initiation was performed. Pre-treatment patient- and cancer-related characteristics were recorded. Survival data in addition to gastrostomy tube utilization, swallowing function, and hematologic toxicity were captured.
Eighty-nine patients treated between 1997 and 2009 were eligible for analysis (median age, 76 years; range, 70–94; male, 61%; ECOG PS, 0–1 43%; stage IVA/B, 71%). 86 were evaluable for survival analysis. 5-year overall and event-free survival were both at 32% with a median follow-up time of 39.2 months. The majority (86.5%) were able to complete all planned treatment cycles. A significant proportion of patients, however, required gastrostomy tube during CRT (62%) and developed aspiration during swallowing evaluation post-treatment (44%). Several patients required hospice (9%) or skilled nursing facility (13%) referrals during treatment.
Select older adults with LA-HNC can still experience long-term benefits despite 5-year survival rates lower than those historically reported in younger patients undergoing identical CRT regimens although potentially at higher risk for acute toxicities. Assessment and selection of those who can tolerate more intense combined-modality strategies and their long-term outcomes merit further larger, prospective studies.
Journal of Geriatric Oncology 01/2013; 4(4):327–333. · 1.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
AdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC).MethodsTNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 10(9) to 4 10(11 )PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment.ResultsFourteen patients were treated. DLT was reached at a dose level of 3 (4 10(11 )PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient.ConclusionsTNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 10(10 )PU. Monitoring for thrombotic events is indicated.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Current standard therapy for nasopharyngeal carcinoma (NPC) is concurrent chemoradiation based on randomized data. However, limited randomized data exist to support the addition of induction chemotherapy (ICT). METHODS: 58 Patients with NPC were treated from 1990 to 2010. All patients received platinum-based ICT. All 58 patients were treated with chemoradiation, 57 in a week-on/week-off (WOWO) fashion. Concurrent chemotherapy included hydroxyurea/5-fluorouracil for all patients. Median radiation dose was 70Gy. No patient received adjuvant chemotherapy. RESULTS: AJCC 2009 stage was II=13, III=21, IVa=13, and IVb=11. Median follow-up for surviving patients was 66months. Response to ICT was complete response (CR) 17% and partial response (PR) 64%. The CR rate after chemoradiation was 96%. Five-year actuarial freedom from local failure (FFLF), freedom from distant failure (FFDF), cause-specific survival (CSS), and overall survival (OS) was 98%, 90%, 90%, and 76%, respectively. Analysis of pediatric patients (n=9) demonstrated 5-year actuarial FFLF, FFDF, CSS, and OS of 100%, 88%, 80%, and 80%, respectively. CONCLUSIONS: ICT followed by concurrent chemoradiation demonstrates excellent FFLF, FFDF, CSS, and OS with tolerable toxicity. Induction chemotherapy followed by concurrent chemoradiation for patients with NPC should be explored further in a randomized setting.
[Show abstract][Hide abstract] ABSTRACT: Organ-sparing approaches with chemoradiotherapy are often used in the treatment of patients with laryngeal cancer, and the oncologic outcomes of these patients are similar to patients who undergo laryngectomy. However, chemoradiotherapy for laryngeal cancer patients with large or locally-invasive (T4) tumors has been more slowly incorporated due to concern for poor post-treatment function of the preserved larynx. Here, we characterize acute and long-term performance and quality-of-life (QOL) outcomes of T4 laryngeal cancer patients treated with induction chemotherapy followed by combined chemoradiotherapy. Using several validated metrics, we find patients experience a decline in most measures of performance and QOL during and immediately following treatment. However, the majority of patients improve to baseline over varying lengths of time following completion of treatment, and many go on to exceed pre-treatment levels of function. Gender, race, alcohol, and tobacco usage were found to be associated with differences in performance and QOL scores across time points. This study suggests that patients with advanced laryngeal tumors who historically had been considered poor candidates for organ-sparing treatment are able to return to, and in many cases exceed pre-treatment performance and QOL following induction chemotherapy and combined chemoradiotherapy.
[Show abstract][Hide abstract] ABSTRACT: Outcomes data treating patients with oligometastatic (≤ 5 metastases) non-small cell lung carcinoma (NSCLC) with hypofractionated image-guided radiotherapy (HIGRT) are limited.
Consecutive oligometastatic NSCLC patients were reviewed from a prospective database. Patients were included if all active diseases were treated with HIGRT. Lesions that had received prior radiation or had radiographic/metabolic resolution after chemotherapy were not treated with HIGRT. Local control of all treated lesions, distant control, progression-free survival (PFS), overall survival (OS), and control of individual lesions (LeC) were calculated.
Twenty-five patients with median of 2 treated oligometastatic lesions were included. Median follow-up was 14 months. Median age was 66 years. Nineteen patients received systemic therapy before HIGRT and 11 had progressive disease after their most recent systemic therapy before HIGRT. Median OS and PFS were 22.7 and 7.6 months. The 18 months local control, distant control, OS, and PFS were 66.1%, 31.7%, 52.9%, and 28.0%. Greater than two sites treated with HIGRT, nonadenocarcinoma histology, prior systemic therapy, and progression after systemic therapy were associated with worse PFS. Sixty-two individual lesions of median size 2.7 cm were treated. For extracranial lesions, median total and fraction dose were 50 and 5 Gy. Median standard equivalent dose in 2 Gy fractions for extracranial lesions was 64.6 Gy yielding 18 months LeC of 70.7%. Standard equivalent dose ≥64.6 Gy increased LeC (p = 0.04). Two patients experienced grade 3 toxicity.
HIGRT for oligometastatic NSCLC provides durable LeC and may provide long-term PFS in some patients. Future HIGRT studies should optimize patient selection and integration with systemic therapy.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2011; 7(2):376-81. · 4.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A woman suffering from cancer presented with headache, confusion, and blurred and double vision with an unsteady gait. Magnetic resonance imaging and lumbar puncture were normal. Subsequently her visual loss and mental status worsened: examination then revealed moderate confusion; light perception vision bilaterally; upbeat nystagmus in primary gaze with gaze evoked vertical and horizontal nystagmus; and disc swelling with retinal haemorrhages. Repeat magnetic resonance imaging showed changes in her thalami, caudate, periaqueductal gray matter, and tectum. A serum thiamine level was measured and she was treated with thiamine replacement for Wernicke encephalopathy. She had near complete recovery of vision, mentation, and eye movements. Optical coherence tomography showed swelling of the retinal nerve layer, and visually evoked potential demonstrated delayed signals consistent with optic nerve demyelination. The case is the first to demonstrate rapid onset of imaging changes having a documented normal scan nine days previously.
[Show abstract][Hide abstract] ABSTRACT: Patients with T4 laryngeal cancers, including those with large-volume (cartilage or tongue-base invasion) lesions, are often excluded from organ-preservation trials due to expectations of inferior outcome in terms of survival and function. We hypothesize that such patients indeed have acceptable survival and function when treated with organ-preservation strategies.
Retrospective analysis of prospectively collected data of a cohort of patients with T4 laryngeal cancer was carried out. Follow-up ranged from 0.18 to 15.6 years. All T4 laryngeal cancer patients who were enrolled in the University of Chicago concomitant chemoradiotherapy protocols from 1994 to the present were reviewed. This study was composed of 80 newly diagnosed T4 laryngeal cancer patients. Efficacy of treatment was determined through evaluations of survival and function. Survival was evaluated via Kaplan-Meier methods. Swallowing function was evaluated by an oropharyngeal motility (OPM) study and swallowing scores were assigned. Higher scores reflected increasing swallowing dysfunction.
Fifty-five of 80 patients (~69%) had documented large-volume tumor. Two- and 5-year overall survivals were 60.0% and 48.7%, respectively. Disease-specific 2- and 5-year survivals for the group were 80.1% and 71.3%, and 79.4 and 74.3%, respectively, for the 55 patients with large volume status. Progression-free survival rates were 52.6% and 47.6%. Forty-four of 65 patients (~68%) with OPM data had a Swallowing Performance Status Scale (SPSS) score of ≤5, indicating various degrees of swallowing abnormalities not requiring a gastrostomy tube. This is a functional-preservation rate of 67.7%.
Chemoradiation for patients with T4 laryngeal cancer appears to be an effective and reasonable option, particularly in light of the satisfactory survival and function-preservation rates.
Head & Neck 11/2011; 34(8):1162-7. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A subset of patients with metastatic cancer in limited organs may benefit from metastasis-directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis-directed radiotherapy.
Patients with 1 to 5 metastatic cancer sites with a life expectancy of >3 months received escalating stereotactic body radiotherapy (SBRT) doses to all known cancer sites. Patients were followed radiographically with CT scans of the chest, abdomen, and pelvis and metabolically with fluorodeoxyglucose-positron emission tomography, 1 month after treatment, and then every 3 months. Acute toxicities were scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0, and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system.
Sixty-one patients with 113 metastases were enrolled from November 2004 to November 2009 on a prospective radiation dose escalation study. Median follow-up was 20.9 months. Patients tolerated treatment well; the maximal tolerated dose was not reached in any cohort. Eleven patients (18.3%) have not progressed. One and 2-year progression-free survival are 33.3% (95% confidence interval [CI], 22.8-46.1) and 22.0% (95% CI, 12.8-34.4); 1-year and 2-year overall survival are 81.5% (95% CI, 71.1-91.1) and 56.7% (95% CI, 43.9-68.9). Seventy-two percent of patients whose tumors progressed did so in limited (1-3) metastatic sites.
Patients with 1 to 5 metastases can be safely treated to multiple body sites and may benefit from SBRT. Further investigation should focus on patient selection.
Cancer 10/2011; 118(11):2962-70. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy.
From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m² on d1), infusional 5-fluorouracil (600 mg/m²/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment.
Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1).
Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.
Head & Neck Oncology 07/2011; 3:31. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment of technically operable, medically fit locoregionally advanced non-small cell lung cancer (NSCLC) patients is a controversial therapeutic challenge. Our group routinely uses a trimodality approach. Recent advances in radiotherapy allow for improved tumor targeting and daily patient positioning. We hypothesized that these technologies would improve pathologic response rates. We analyzed consecutively treated stage IIIA/IIIB NSCLC patients undergoing chemoradiotherapy before major lung resection, with particular attention paid to the impact of advanced technologies.
Locoregionally advanced NSCLC patients (N2) staged in a multidisciplinary forum with mediastinoscopy were planned to receive platinum-based chemotherapy and 60Gy and major lung resection. Four-dimensional CT (4DCT) and image-guided radiotherapy (IGRT) were used as available. Survival endpoints were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models.
We identified 53 patients from 2/1999 to 2/2010. Median RT dose was 59Gy. 68% underwent lobectomy. Forty-three patients were downstaged pathologically (81%), 38 experienced mediastinal sterilization (72%), and 21 (40%) had complete pathologic response (pCR). 1 and 2 year OS were 85.5% and 61.6%. Superior OS and DFS were associated with nodal downstaging and mediastinal sterilization (pN0). Treatment with IGRT/4DCT in 10 patients resulted in high rates of nodal downstaging (100% vs 77%, p=0.0452), mediastinal sterilization (90% vs 67%, p=0.0769), and pCR (60% vs 35%, p=0.0728).
In selected patients, definitive dose CRT followed by major lung resection results in promising DFS and OS. The use of advanced radiotherapy techniques (4DCT and IGRT) appears to result in promising pathologic response rates.
Lung cancer (Amsterdam, Netherlands) 06/2011; 74(3):446-50. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report outcomes of oral cavity cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy (chemoIMRT).
Between 2001 and 2004, 21 patients with oral cavity squamous cell carcinoma underwent definitive chemoIMRT. Sites included were oral tongue (n = 9), floor of mouth (n = 6), buccal mucosa (n = 3), retromolar trigone (n = 2), and hard palate (n = 1). Most had stage III-IV disease (n = 20). The most common regimen was 5 days infusional 5-fluorouracil (600 mg/m(2)/d × 5 days), hydroxyurea (500 mg, PO BID), and 1.5 Gy twice-daily irradiation to 72 to 75 Gy.
The median follow-up for surviving patients was 60 months. Treatment failure occurred as follows: local-1, regional-1, and distant metastases-2. The 2- and 5-year estimates of locoregional progression-free survival, disease-free survival, and overall survival were 90% and 90%, 71% and 71%, and 76% and 76%, respectively. Late complications included osteoradionecrosis (3 patients, 14%).
Concurrent chemoIMRT results in promising locoregional control for oral cavity squamous cell carcinomas with acceptable toxicity.
American journal of clinical oncology 05/2011; 34(4):356-61. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Concurrent chemoreirradiation therapy (CRRT) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that response to induction chemotherapy (IC) would improve outcome and predict increased survival.
Subjects with recurrent SCCHN not amenable to standard therapy were eligible. IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14, followed by surgical resection, if appropriate, and/or CRRT consisting of carboplatin, pemetrexed, and single daily fractionated radiotherapy.
Thirty-five subjects were enrolled, 31 were assessable for response, with 11 responders [response rate = 35%; 95% confidence interval (CI) 19.2-54.6]. Among 24 subjects who started CRRT, 11 were assessable for radiographic response, 4 complete response, 2 partial response, and 5 progressive disease. Median progression-free survival and overall survival (OS) were 5.5 months (95% CI 3.6-8.3) and 9.5 months (95% CI 7.2-15.4), respectively. One-year OS was 43% (95% CI 26% to 58%). Subjects who responded to IC had improved survival (P = 0.02). Toxic effects included mucositis, dermatitis, neutropenia, infection, hemorrhage, dehydration, and pain.
The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN. Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT.
Annals of Oncology 03/2011; 22(11):2501-7. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Outstanding work on the cellular and molecular aspects of radioresistance has been published in the past 10 years [1,2]. The work presented herein does not attempt to be comprehensive but is a review of the work of our laboratory as it pertains
to aspects of radioresistance with potential applicability to chemotherapy/cytokine radiotherapy interactions.
[Show abstract][Hide abstract] ABSTRACT: We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC).
Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m(2)/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy.
Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen.
Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.
Annals of Oncology 02/2011; 22(10):2304-9. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: to identify factors that influence patient-centered measures of speech and swallowing function after successful use of chemoradiotherapy to treat cancers of the head and neck.
patients previously enrolled in a phase 2 trial using induction chemotherapy consisting of carboplatin and paclitaxel followed by chemoradiotherapy with paclitaxel, fluorouracil, hydroxyurea, and 1 of 3 radiation dose levels were assigned speaking and swallowing scores at follow-up ranging from 1 to 4, with 1 representing normal speech or swallowing and 4 representing significant sustained deficits.
one hundred eighty-four patients with locoregionally advanced head and neck cancer.
speech and swallowing function after chemoradiotherapy.
of the 222 patients originally enrolled in the trial, 184 were alive and free of locoregional recurrence at the outset of this study. Of these eligible patients, 163 (88.6%) were assigned a speaking score of 1 through 4 at an average of 34.8 (range, 1.5-76.4) months after completion of treatment, whereas 166 patients (90.2%) were assigned a swallowing score of 1 through 4 at an average of 34.5 (range, 1.0-76.4) months after completion of treatment. Most patients (84.7% with speaking scores and 63.3% with swallowing scores) had no residual deficit and were assigned scores of 1. Factors that were associated with worse speaking outcomes included female sex, smoking history, hypopharyngeal or laryngeal primary sites, and poor response to induction chemotherapy; factors associated with worse swallowing outcomes included advanced patient age, poor performance status, primary site, and neck dissection.
among patients successfully treated for locoregionally advanced cancers of the head and neck, several factors correlate with speaking and swallowing outcomes. Because advances in therapy have led to improved survival in these patients, understanding and controlling adverse effects of treatment should continue to be an active area of investigation.
Archives of otolaryngology--head & neck surgery 12/2010; 136(12):1226-34. · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear.
Forty-one postoperative patients with stage III-IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy.
After a median follow-up of 72 months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p=0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay.
Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation.
Radiotherapy and Oncology 10/2010; 97(2):318-21. · 4.52 Impact Factor