Publications by authors named "Jimmy J Caudell"

76 Publications

Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments.

Int J Radiat Oncol Biol Phys 2021 May 11;110(1):147-159. Epub 2021 Feb 11.

Department of Radiation Oncology, Bon Secours Mercy Health System, Youngstown, Ohio.

Purpose: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized.

Methods And Materials: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed.

Results: Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT.

Conclusions: Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.037DOI Listing
May 2021

Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002).

J Clin Oncol 2021 Mar 28;39(9):956-965. Epub 2021 Jan 28.

Stanford University, Stanford, CA.

Purpose: Reducing radiation treatment dose could improve the quality of life (QOL) of patients with good-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). Whether reduced-dose radiation produces disease control and QOL equivalent to standard chemoradiation is not proven.

Patients And Methods: In this randomized, phase II trial, patients with p16-positive, T1-T2 N1-N2b M0, or T3 N0-N2b M0 OPSCC (7th edition staging) with ≤ 10 pack-years of smoking received 60 Gy of intensity-modulated radiation therapy (IMRT) over 6 weeks with concurrent weekly cisplatin (C) or 60 Gy IMRT over 5 weeks. To be considered for a phase III study, an arm had to achieve a 2-year progression-free survival (PFS) rate superior to a historical control rate of 85% and a 1-year mean composite score ≥ 60 on the MD Anderson Dysphagia Inventory (MDADI).

Results: Three hundred six patients were randomly assigned and eligible. Two-year PFS for IMRT + C was 90.5% rejecting the null hypothesis of 2-year PFS ≤ 85% ( = .04). For IMRT, 2-year PFS was 87.6% ( = .23). One-year MDADI mean scores were 85.30 and 81.76 for IMRT + C and IMRT, respectively. Two-year overall survival rates were 96.7% for IMRT + C and 97.3% for IMRT. Acute adverse events (AEs) were defined as those occurring within 180 days from the end of treatment. There were more grade 3-4 acute AEs for IMRT + C (79.6% 52.4%; < .001). Rates of grade 3-4 late AEs were 21.3% and 18.1% ( = .56).

Conclusion: The IMRT + C arm met both prespecified end points justifying advancement to a phase III study. Higher rates of grade ≥ 3 acute AEs were reported in the IMRT + C arm.
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http://dx.doi.org/10.1200/JCO.20.03128DOI Listing
March 2021

Evaluating compliance with process-related quality metrics and survival in oral cavity squamous cell carcinoma: Multi-institutional oral cavity collaboration study.

Head Neck 2021 Jan 12;43(1):60-69. Epub 2020 Sep 12.

Head and Neck Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: Process-related measures have been proposed as quality metrics in head and neck cancer care. A recent single-institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi-institutional cohort.

Methods: Multicenter retrospective study of patients with oral cavity squamous cell (1/2005-1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) was evaluated using Cox proportional hazards models.

Results: Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival.

Conclusions: Process-related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi-institutional cohort.
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http://dx.doi.org/10.1002/hed.26454DOI Listing
January 2021

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 07;18(7):873-898

29National Comprehensive Cancer Network.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.
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http://dx.doi.org/10.6004/jnccn.2020.0031DOI Listing
July 2020

Alterations in genetic pathways following radiotherapy for head and neck cancer.

Head Neck 2020 02 13;42(2):312-320. Epub 2019 Dec 13.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: Radiotherapy (RT) is an integral component in the treatment of head and neck cancer (HNC).We hypothesized there would be alterations in gene-expression and pathway activity in HNC samples obtained in recurrent HNC that were previously treated with RT, when compared to RT-naïve disease.

Methods: Patient data was abstracted from a prospectively maintained database. Linear-microarray analysis and supervised gene-set enrichment-analysis were employed to compare RT-naive and recurrent disease after prior-RT.

Results: A total of 157 patients were analyzed, 96 (61%) were RT-naive and 61 (39%) had RT.After radiation, there was upregulation of genes associated with angiogenesis, protein-translation-machinery, cell-cycle regulation, and growth factors, and downregulation associated with Myc activity, and hypoxic response (all P < .001).Previously irradiated HNC was associated with downregulation in 19/42 genes in the Wnt/B-catenin-pathway (P = .045)and 119/199 genes involved in the MYC target pathway (P = .024).

Conclusion: Patients with recurrences salvaged surgically post-RT had significant alterations in gene-expression and in Wnt/B-catenin and MYC-target pathways. These pathways may represent potential targets to prevent development of resistance to RT.
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http://dx.doi.org/10.1002/hed.26004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771332PMC
February 2020

The importance of dead material within a tumour on the dynamics in response to radiotherapy.

Phys Med Biol 2020 01 10;65(1):015007. Epub 2020 Jan 10.

Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom. Author to whom correspondence should be addressed.

In vivo tumours are highly heterogeneous, often comprising regions of hypoxia and necrosis. Radiotherapy significantly alters the intratumoural composition. Moreover, radiation-induced cell death may occur via a number of different mechanisms that act over different timescales. Dead material may therefore occupy a significant portion of the tumour volume for some time after irradiation and may affect the subsequent tumour dynamics. We present a three phase tumour growth model that accounts for the effects of radiotherapy and use it to investigate how dead material within the tumour may affect the spatio-temporal tumour response dynamics. We use numerical simulation of the model equations to characterise qualitatively different tumour volume dynamics in response to fractionated radiotherapy. We demonstrate examples, and associated parameter values, for which the properties of the dead material significantly alter the observed tumour volume dynamics throughout treatment. These simulations suggest that for some cases it may not be possible to accurately predict radiotherapy response from pre-treatment, gross tumour volume measurements without consideration of the dead material within the tumour.
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http://dx.doi.org/10.1088/1361-6560/ab4c27DOI Listing
January 2020

Integrating Mathematical Modeling into the Roadmap for Personalized Adaptive Radiation Therapy.

Trends Cancer 2019 08 10;5(8):467-474. Epub 2019 Jul 10.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

In current radiation oncology practice, treatment protocols are prescribed based on the average outcomes of large clinical trials, with limited personalization and without adaptations of dose or dose fractionation to individual patients based on their individual clinical responses. Predicting tumor responses to radiation and comparing predictions against observed responses offers an opportunity for novel treatment evaluation. These analyses can lead to protocol adaptation aimed at the improvement of patient outcomes with better therapeutic ratios. We foresee the integration of mathematical models into radiation oncology to simulate individual patient tumor growth and predict treatment response as dynamic biomarkers for personalized adaptive radiation therapy (RT).
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http://dx.doi.org/10.1016/j.trecan.2019.06.006DOI Listing
August 2019

Challenges With the 8th Edition of the AJCC Cancer Staging Manual for Breast, Testicular, and Head and Neck Cancers.

J Natl Compr Canc Netw 2019 05;17(5.5):560-564

Three experts discussed changes in the 8th edition of the AJCC Cancer Staging Manual and challenges regarding these changes for staging of breast cancer, testicular cancer, and head and neck cancer, respectively. In general, the staging changes for breast cancer and for human papillomavirus-positive oropharyngeal cancer were hailed as improvements, but the changes for testicular cancer were questioned as to their clinical relevance. Better studies are needed to improve staging for human papillomavirus-negative oropharyngeal cancer.
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http://dx.doi.org/10.6004/jnccn.2019.5015DOI Listing
May 2019

Oral gargle-tumor biopsy human papillomavirus (HPV) agreement and associated factors among oropharyngeal squamous cell carcinoma (OPSCC) cases.

Oral Oncol 2019 05 3;92:85-91. Epub 2019 Apr 3.

Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, United States. Electronic address:

Objective: Assess oral gargle-tumor human papillomavirus (HPV) agreement among oropharyngeal squamous cell carcinoma (OPSCC) cases by several disease characteristics.

Materials And Methods: 171 treatment naïve OPSCC were enrolled 2014-2017. Tumors were categorized as early or late disease with early disease defined as T1-2 with no nodal involvement or at most a single ipsilateral positive node <3 cm. Oral gargle samples were obtained via a 30-second rinse and gargle. The RHA Kit HPV SP-LiPA was utilized for HPV genotyping of tumor (FFPE) and oral gargle specimens. Sensitivity, specificity, positive and negative predictive value, percent agreement, and 95% exact binomial confidence intervals were estimated. Multivariable logistic regression models were fit to predict agreement.

Results: 83.0% and 93.0% of oral gargle and tumor specimens were HPV positive. Oral gargle-tumor agreement for any oncogenic HPV type and HPV 16 was 73.7%. High oncogenic HPV oral gargle-tumor agreement was observed for late disease presentation, p16 positive cases, and tumors at the tonsils (74.5-80.8%). Similar trends were observed for HPV 16. Agreement for any oncogenic HPV and HPV 16 was significantly higher for late vs. early disease (77.9% vs 57.1%, p = 0.01). Oral gargle-tumor oncogenic HPV and HPV 16 agreement was independently associated with age ≥50 years and late disease presentation.

Conclusion: Overall, oral-tumor HPV agreement among OPSCC was relatively high. However, oral-tumor HPV agreement was significantly lower among younger cases and those diagnosed with earlier disease. Additional biomarkers are needed to improve oral HPV test characteristics to identify OPSCC early.
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http://dx.doi.org/10.1016/j.oraloncology.2019.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736648PMC
May 2019

A competing risk nomogram to predict severe late toxicity after modern re-irradiation for squamous carcinoma of the head and neck.

Oral Oncol 2019 03 8;90:80-86. Epub 2019 Feb 8.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Purpose: Severe late toxicity is common after re-irradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck. However, many patients experience complications from tumor progression before manifesting late effects. We constructed a nomogram to examine this relationship between late toxicity and competing risks.

Methods And Materials: Patients with RSP squamous carcinoma originating in a field previously irradiated to ≥40 Gy and treated with IMRT-based re-irradiation to ≥40 Gy were collected. Grade ≥3 late toxicity developing ≥90 days after re-irradiation was collected. A multivariable competing-risk model was fit to the actuarial risk of late toxicity with progression or death as the competing risk. The final bootstrap optimized model was converted into a nomogram.

Results: From 9 institutions, 505 patients were included. The 2-year incidence of grade ≥3 late toxicity was 16.7% (95% CI 13.2-20.2%) whereas progression or death was 64.2% (95% CI 59.7-68.8%). The median freedom from late toxicity, progression or death was 10.7, 5.5 and 3.2 months for RPA class I-III patients respectively, whereas the median OS was 44.9, 15.9 and 7.9 months, respectively. The final model included six clinical factors. Notably, dose, volume and fractionation did not significantly impact toxicity.

Conclusions: After re-irradiation, the risk of progression or death is approximately four times the risk of radiation-related severe late toxicity. The risk of late toxicity may be more dependent on patient and disease factors than modifiable treatment factors. This model is useful for patient selection, pre-treatment consent and post-treatment survivorship following re-irradiation.
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http://dx.doi.org/10.1016/j.oraloncology.2019.01.022DOI Listing
March 2019

Proliferation saturation index in an adaptive Bayesian approach to predict patient-specific radiotherapy responses.

Int J Radiat Biol 2019 10 19;95(10):1421-1426. Epub 2019 Mar 19.

Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute , Tampa , FL , USA.

Radiotherapy prescription dose and dose fractionation protocols vary little between individual patients having the same tumor grade and stage. To personalize radiotherapy a predictive model is needed to simulate radiation response. Previous modeling attempts with multiple variables and parameters have been shown to yield excellent data fits at the cost of non-identifiability and clinically unrealistic results. We develop a mathematical model based on a proliferation saturation index (PSI) that is a measurement of pre-treatment tumor volume-to-carrying capacity ratio that modulates intrinsic tumor growth and radiation response rates. In an adaptive Bayesian approach, we utilize an increasing number of data points for individual patients to predict patient-specific responses to subsequent radiation doses. Model analysis shows that using PSI as the only patient-specific parameter, model simulations can fit longitudinal clinical data with high accuracy (=0.84). By analyzing tumor response to radiation using daily CT scans early in the treatment, response to the remaining treatment fractions can be predicted after two weeks with high accuracy (c-index = 0.89). The PSI model may be suited to forecast treatment response for individual patients and offers actionable decision points for mid-treatment protocol adaptation. The presented work provides an actionable image-derived biomarker prior to and during therapy to personalize and adapt radiotherapy.
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http://dx.doi.org/10.1080/09553002.2019.1589013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081883PMC
October 2019

Novel Genomic-Based Strategies to Personalize Lymph Node Radiation Therapy.

Semin Radiat Oncol 2019 04;29(2):111-125

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL; Departments of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL. Electronic address:

Current standard radiotherapy doses have been derived from empiric methods rather than a scientific framework. Subclinical nodal dosing remains relatively uniform across most disease sites, despite heterogeneity in patient and tumor biology. It is now clear that there are subsets of patients who will benefit from genomically-informed radiotherapy planning, and there are increasing efforts toward prescribing radiation dose to match the radiosensitivity of the tumor. By using novel genomic biomarkers to personalize delivery of radiotherapy, there is an opportunity to improve loco-regional control and cure rates. We survey the current landscape of personalized radiation oncology across commonly treated disease sites.
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http://dx.doi.org/10.1016/j.semradonc.2018.11.003DOI Listing
April 2019

Interferon is associated with improved survival for node-positive cutaneous melanoma: a single-institution experience.

Melanoma Manag 2018 Jun 9;5(1):MMT02. Epub 2018 Apr 9.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.

Aim: We assessed the role of adjuvant interferon on relapse-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) in node-positive melanoma patients.

Methods: We retrospectively reviewed 385 node-positive patients without distant metastatic disease treated from 1998 to 2015. The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph node biopsy ± completion LND (n = 270). 128 patients (33.2%) received adjuvant interferon.

Results: After a median follow-up of 70 months, interferon was associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR: 0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal stage, node size, sex, primary site, adjuvant therapy and extracapsular extension. In an exploratory age-matched comparison of patients treated with (n = 67) and without (n = 233) adjuvant immunotherapy, interferon still showed improved RFS, DMFS and OS.

Conclusion: Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.
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http://dx.doi.org/10.2217/mmt-2017-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122528PMC
June 2018

Patient choice for high-volume center radiation impacts head and neck cancer outcome.

Cancer Med 2018 10 2;7(10):4964-4979. Epub 2018 Sep 2.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

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.
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http://dx.doi.org/10.1002/cam4.1756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198196PMC
October 2018

Temporally feathered intensity-modulated radiation therapy: A planning technique to reduce normal tissue toxicity.

Med Phys 2018 Jul 8;45(7):3466-3474. Epub 2018 Jun 8.

Department of Radiation Oncology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.

Purpose: Intensity-modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy "temporally feathered radiation therapy" (TFRT).

Methods: Temporally feathered radiotherapy plans were generated as a composite of five simulated treatment plans each with altered constraints on particular hypothetical organs at risk (OARs) to be delivered sequentially. For each of these TFRT plans, OARs chosen for feathering receive higher doses while the remaining OARs receive lower doses than the standard fractional dose delivered in a conventional fractionated IMRT plan. Each TFRT plan is delivered a specific weekday, which in effect leads to a higher dose once weekly followed by four lower fractional doses to each temporally feathered OAR. We compared normal tissue toxicity between TFRT and conventional fractionated IMRT plans by using a dynamical mathematical model to describe radiation-induced tissue damage and repair over time.

Results: Model-based simulations of TFRT demonstrated potential for reduced normal tissue toxicity compared to conventionally planned IMRT. The sequencing of high and low fractional doses delivered to OARs by TFRT plans suggested increased normal tissue recovery, and hence less overall radiation-induced toxicity, despite higher total doses delivered to OARs compared to conventional fractionated IMRT plans. The magnitude of toxicity reduction by TFRT planning was found to depend on the corresponding standard fractional dose of IMRT and organ-specific recovery rate of sublethal radiation-induced damage.

Conclusions: TFRT is a novel technique for treatment planning and optimization of therapeutic radiotherapy that considers the nonlinear aspects of normal tissue repair to optimize toxicity profiles. Model-based simulations of TFRT to carefully conceptualized clinical cases have demonstrated potential for radiation-induced toxicity reduction in a previously described dynamical model of normal tissue complication probability (NTCP).
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http://dx.doi.org/10.1002/mp.12988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041138PMC
July 2018

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

J Natl Compr Canc Netw 2018 05;16(5):479-490

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.
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http://dx.doi.org/10.6004/jnccn.2018.0026DOI Listing
May 2018

Radiosensitivity of Lung Metastases by Primary Histology and Implications for Stereotactic Body Radiation Therapy Using the Genomically Adjusted Radiation Dose.

J Thorac Oncol 2018 08 5;13(8):1121-1127. Epub 2018 May 5.

Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address:

Introduction: We assessed the radiosensitivity of lung metastases on the basis of primary histologic type by using a validated gene signature and model lung metastases for the gnomically adjusted radiation dose (GARD).

Methods: Tissue samples were identified from our prospective observational protocol. The radiosensitivity index (RSI) 10-gene assay was run on samples and calculated alongside the GARD by using the previously published algorithms. A cohort of 105 patients with 137 lung metastases treated with stereotactic body radiation therapy (SBRT) at our institution was used for clinical correlation.

Results: A total of 138 unique metastatic lung lesions from our institution's tissue biorepository were identified for inclusion. There were significant differences in the RSI of lung metastases on the basis of histology. In order of decreasing radioresistance, the median RSIs for the various histologic types of cancer were endometrial adenocarcinoma (0.49), soft-tissue sarcoma (0.47), melanoma (0.44), rectal adenocarcinoma (0.43), renal cell carcinoma (0.33), head and neck squamous cell cancer (0.33), colon adenocarcinoma (0.32), and breast adenocarcinoma (0.29) (p = 0.002). We modeled the GARD for these samples and identified the biologically effective dose necessary to optimize local control. The 12- and 24-month Kaplan-Meier rates of local control for radioresistant versus radiosensitive histologic types from our clinical correlation cohort after lung SBRT were 92%/87% and 100%, respectively (p = 0.02).

Conclusions: In this analysis, we have noted significant differences in radiosensitivity on the basis of primary histologic type of lung metastases and have modeled the biologically effective dose necessary to optimize local control. This study suggests that primary histologic type may be an additional factor to consider in selection of SBRT dose to the lung and that dose personalization may be feasible.
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http://dx.doi.org/10.1016/j.jtho.2018.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810135PMC
August 2018

Volume, Dose, and Fractionation Considerations for IMRT-based Reirradiation in Head and Neck Cancer: A Multi-institution Analysis.

Int J Radiat Oncol Biol Phys 2018 03 1;100(3):606-617. Epub 2017 Dec 1.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Purpose: Limited data exist to guide the treatment technique for reirradiation of recurrent or second primary squamous carcinoma of the head and neck. We performed a multi-institution retrospective cohort study to investigate the effect of the elective treatment volume, dose, and fractionation on outcomes and toxicity.

Methods And Materials: Patients with recurrent or second primary squamous carcinoma originating in a previously irradiated field (≥40 Gy) who had undergone reirradiation with intensity modulated radiation therapy (IMRT); (≥40 Gy re-IMRT) were included. The effect of elective nodal treatment, dose, and fractionation on overall survival (OS), locoregional control, and acute and late toxicity were assessed. The Kaplan-Meier and Gray's competing risks methods were used for actuarial endpoints.

Results: From 8 institutions, 505 patients were included in the present updated analysis. The elective neck was not treated in 56.4% of patients. The median dose of re-IMRT was 60 Gy (range 39.6-79.2). Hyperfractionation was used in 20.2%. Systemic therapy was integrated for 77.4% of patients. Elective nodal radiation therapy did not appear to decrease the risk of locoregional failure (LRF) or improve the OS rate. Doses of ≥66 Gy were associated with improvements in both LRF and OS in the definitive re-IMRT setting. However, dose did not obviously affect LRF or OS in the postoperative re-IMRT setting. Hyperfractionation was not associated with improved LRF or OS. The rate of acute grade ≥3 toxicity was 22.1% overall. On multivariable logistic regression, elective neck irradiation was associated with increased acute toxicity in the postoperative setting. The rate of overall late grade ≥3 toxicity was 16.7%, with patients treated postoperatively with hyperfractionation experiencing the highest rates.

Conclusions: Doses of ≥66 Gy might be associated with improved outcomes in high-performance patients undergoing definitive re-IMRT. Postoperatively, doses of 50 to 66 Gy appear adequate after removal of gross disease. Hyperfractionation and elective neck irradiation were not associated with an obvious benefit and might increase toxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2017.11.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269162PMC
March 2018

More Information Needed, Surgery Provides It.

Int J Radiat Oncol Biol Phys 2017 12 24;99(5):1061-1062. Epub 2017 Aug 24.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

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http://dx.doi.org/10.1016/j.ijrobp.2017.08.016DOI Listing
December 2017

A Multi-institutional Comparison of SBRT and IMRT for Definitive Reirradiation of Recurrent or Second Primary Head and Neck Cancer.

Int J Radiat Oncol Biol Phys 2018 03 24;100(3):595-605. Epub 2017 Apr 24.

Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Division of Head and Neck Surgery, Department of Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Electronic address:

Purpose: Two modern methods of reirradiation, intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), are established for patients with recurrent or second primary squamous cell carcinoma of the head and neck (rSCCHN). We performed a retrospective multi-institutional analysis to compare methods.

Methods And Materials: Data from patients with unresectable rSCCHN previously irradiated to ≥40 Gy who underwent reirradiation with IMRT or SBRT were collected from 8 institutions. First, the prognostic value of our IMRT-based recursive partitioning analysis (RPA) separating those patients with unresectable tumors with an intertreatment interval >2 years or those with ≤2 years and without feeding tube or tracheostomy dependence (class II) from other patients with unresected tumors (class III) was investigated among SBRT patients. Overall survival (OS) and locoregional failure were then compared between IMRT and SBRT by use of 2 methods to control for baseline differences: Cox regression weighted by the inverse probability of treatment and subset analysis by RPA classification.

Results: The study included 414 patients with unresectable rSCCHN: 217 with IMRT and 197 with SBRT. The unadjusted 2-year OS rate was 35.4% for IMRT and 16.3% for SBRT (P<.01). Among SBRT patients, RPA classification retained an independent association with OS. On Cox regression weighted by the inverse probability of treatment, no significant differences in OS or locoregional failure between IMRT and SBRT were demonstrated. Analysis by RPA class showed similar OS between IMRT and SBRT for class III patients. In all class II patients, IMRT was associated with improved OS (P<.001). Further subset analysis demonstrated comparable OS when ≥35 Gy was delivered with SBRT to small tumor volumes. Acute grade ≥4 toxicity was greater in the IMRT group than in the SBRT group (5.1% vs 0.5%, P<.01), with no significant difference in late toxicity.

Conclusions: Reirradiation both with SBRT and with IMRT appear relatively safe with favorable toxicity compared with historical studies. Outcomes vary by RPA class, which informs clinical trial design. Survival is poor in class III patients, and alternative strategies are needed.
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http://dx.doi.org/10.1016/j.ijrobp.2017.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418052PMC
March 2018

Refining Patient Selection for Reirradiation of Head and Neck Squamous Carcinoma in the IMRT Era: A Multi-institution Cohort Study by the MIRI Collaborative.

Int J Radiat Oncol Biol Phys 2018 03 17;100(3):586-594. Epub 2017 Jun 17.

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.

Purpose: The therapeutic ratio of reirradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck may be improved in the intensity modulated radiation therapy (IMRT) era. However, patient selection for reirradiation remains challenging. We performed a multi-institution cohort study to investigate modern outcomes after IMRT-based reirradiation and to identify prognostic subgroups.

Patients And Methods: Patients with RSP squamous carcinoma originating in a previously irradiated field (≥40 Gy) who underwent reirradiation with IMRT (≥40 Gy re-IMRT) were included. Locoregional failure and late toxicity were calculated using the Gray competing risk method. Cox proportional hazards regression was used to identify factors associated with overall survival (OS). Factors associated with OS were entered into a recursive partitioning analysis (RPA) for OS.

Results: From 7 institutions, 412 patients were included. The median dose of re-IMRT was 60 Gy, and the median time between RT courses was 2.4 years. Chemotherapy was used in 76% of patients. The rates of grade ≥3, grade ≥4, and grade 5 acute toxicities were 19%, 4.4%, and 1.2%, respectively. The 2-year cumulative incidence of grade ≥3 late toxicity adjusted for the competing risks of recurrence or death was 14.2%. RPA identified 3 prognostic subgroups with distinct and homogenous OS (P<.001): class I included patients >2 years from their initial course of RT with resected tumors (2-year OS, 61.9%); class II included patients >2 years with unresected tumors or those ≤2 years and without feeding tube or tracheostomy dependence (2-year OS, 40.0%), and the remaining patients formed class III (2-year OS, 16.8%). Fifty-nine percent of class III patients underwent postoperative re-irradiation.

Conclusions: This study informs outcomes and expectations with IMRT-based reirradiation. The RPA classification identifies 3 distinct subgroups, which can guide patient selection for therapy and clinical trial design. RPA class III patients are not ideal candidates for protracted chemoradiation regardless of resection status.
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http://dx.doi.org/10.1016/j.ijrobp.2017.06.012DOI Listing
March 2018

Predicting Patient-Specific Radiotherapy Protocols Based on Mathematical Model Choice for Proliferation Saturation Index.

Bull Math Biol 2018 05 5;80(5):1195-1206. Epub 2017 Jul 5.

Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33647, USA.

Radiation is commonly used in cancer treatment. Over 50% of all cancer patients will undergo radiotherapy (RT) as part of cancer care. Scientific advances in RT have primarily focused on the physical characteristics of treatment including beam quality and delivery. Only recently have inroads been made into utilizing tumor biology and radiobiology to design more appropriate RT protocols. Tumors are composites of proliferating and growth-arrested cells, and overall response depends on their respective proportions at irradiation. Prokopiou et al. (Radiat Oncol 10:159, 2015) developed the concept of the proliferation saturation index (PSI) to augment the clinical decision process associated with RT. This framework is based on the application of the logistic equation to pre-treatment imaging data in order to estimate a patient-specific tumor carrying capacity, which is then used to recommend a specific RT protocol. It is unclear, however, how dependent clinical recommendations are on the underlying tumor growth law. We discuss a PSI framework with a generalized logistic equation that can capture kinetics of different well-known growth laws including logistic and Gompertzian growth. Estimation of model parameters on the basis of clinical data revealed that the generalized logistic model can describe data equally well for a wide range of the generalized logistic exponent value. Clinical recommendations based on the calculated PSI, however, are strongly dependent on the specific growth law assumed. Our analysis suggests that the PSI framework may best be utilized in clinical practice when the underlying tumor growth law is known, or when sufficiently many tumor growth models suggest similar fractionation protocols.
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http://dx.doi.org/10.1007/s11538-017-0279-0DOI Listing
May 2018

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017.

J Natl Compr Canc Netw 2017 06;15(6):761-770

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.
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http://dx.doi.org/10.6004/jnccn.2017.0101DOI Listing
June 2017

Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases.

J Neurooncol 2017 Jun 2;133(2):331-338. Epub 2017 May 2.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902, Magnolia Drive, Tampa, FL, 33612, USA.

Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified. Radiation was administered prior to, during and after anti-PD-1/PD-L1 therapy in 22 lesions (45%), 13 lesions (27%), and 14 lesions (29%), respectively. The 6 months Kaplan-Meier (KM) distant brain control rate was 48% following stereotactic radiation. Six and 12 month KM rates of OS from the date of stereotactic radiation and the date of cranial metastases diagnosis were 48/41% and 81/51%, respectively. The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). A Karnofsky Performance Status (KPS) of <90 was found to be predictive of worse OS following radiation treatment on both univariate and multivariate analyses (MVA, p = 0.01). In our series, stereotactic radiation to NSCLC brain metastases was well tolerated in patients who received anti-PD-1/PD-L1 therapy. Prospective evaluation to determine how these two modalities can be used synergistically to improve distant brain control and OS is warranted.
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http://dx.doi.org/10.1007/s11060-017-2437-5DOI Listing
June 2017

The future of personalised radiotherapy for head and neck cancer.

Lancet Oncol 2017 05 26;18(5):e266-e273. Epub 2017 Apr 26.

Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address:

Radiotherapy has long been the mainstay of treatment for patients with head and neck cancer and has traditionally involved a stage-dependent strategy whereby all patients with the same TNM stage receive the same therapy. We believe there is a substantial opportunity to improve radiotherapy delivery beyond just technological and anatomical precision. In this Series paper, we explore several new ideas that could improve understanding of the phenotypic and genotypic differences that exist between patients and their tumours. We discuss how exploiting these differences and taking advantage of precision medicine tools-such as genomics, radiomics, and mathematical modelling-could open new doors to personalised radiotherapy adaptation and treatment. We propose a new treatment shift that moves away from an era of empirical dosing and fractionation to an era focused on the development of evidence to guide personalisation and biological adaptation of radiotherapy. We believe these approaches offer the potential to improve outcomes and reduce toxicity.
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http://dx.doi.org/10.1016/S1470-2045(17)30252-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771279PMC
May 2017

Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.

J Natl Compr Canc Netw 2017 04;15(4):473-482

Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas

Regional radiation therapy (RT) has been shown to reduce the risk of regional recurrence with node-positive cutaneous melanoma. However, risk factors for regional recurrence, especially in the era of sentinel lymph node biopsy (SLNB), are less clear. Our goals were to identify risk factors associated with regional recurrence and to determine whether a radiosensitivity index (RSI) gene expression signature (GES) could identify patients who experience a survival benefit with regional RT. A single-institution, Institutional Review Board-approved study was performed including 410 patients treated with either SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic LND (n=91). Postoperative regional RT was delivered to the involved nodal basin in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions (range, 5-30). Primary outcomes were regional control and overall survival by RSI GES status. Median follow-up was 69 months (range, 13-180). Postoperative regional RT was associated with a reduced risk of regional recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%; =.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43; <.001). Among higher-risk subgroups, regional RT was associated with a lower risk of regional recurrence among patients with clinically detected lymph nodes (n=175; 5-year regional control: 94.1% vs 69.5%; =.003) and extracapsular extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; <.001). Among a subset of radiated patients with gene expression data available, a low RSI GES (radiosensitive) tumor status was associated with improved survival compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14). Regional RT was associated with a reduced risk of regional recurrence among patients with ECE and clinically detected nodal disease. Gene expression data show promise for better predicting radiocurable patients in the future. In the era of increasingly effective systemic therapies, the value of improved regional control potentially takes on greater significance.
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http://dx.doi.org/10.6004/jnccn.2017.0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771284PMC
April 2017

A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study.

Lancet Oncol 2017 02 18;18(2):202-211. Epub 2016 Dec 18.

Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Electronic address:

Background: Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose.

Methods: We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical outcome in five clinical cohorts: Erasmus Breast Cancer Cohort (n=263); Karolinska Breast Cancer Cohort (n=77); Moffitt Lung Cancer Cohort (n=60); Moffitt Pancreas Cancer Cohort (n=40); and The Cancer Genome Atlas Glioblastoma Patient Cohort (n=98).

Findings: We calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66-172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13-3·94, p=0·018).

Interpretation: A GARD-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology.

Funding: None.
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http://dx.doi.org/10.1016/S1470-2045(16)30648-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771305PMC
February 2017

Adjuvant radiotherapy versus concurrent chemoradiotherapy for the management of high-risk salivary gland carcinomas.

Head Neck 2016 11 21;38(11):1628-1633. Epub 2016 Apr 21.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

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.
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http://dx.doi.org/10.1002/hed.24484DOI Listing
November 2016

Increased acute mortality with chemoradiotherapy for locally advanced head and neck cancer in patients ≥70years.

J Geriatr Oncol 2017 01 3;8(1):50-55. Epub 2016 Oct 3.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jgo.2016.09.003DOI Listing
January 2017

Treatment delays, race, and outcomes in head and neck cancer.

Cancer Epidemiol 2016 Dec 22;45:18-25. Epub 2016 Sep 22.

H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, United States. Electronic address:

Purpose: Patient race has been shown to predict for differences in outcomes and has been attributed to socioeconomic factors such as social support and access to healthcare. In head and neck cancer (HNC), a disease without recommended screening, we sought to investigate the association between race, treatment delays and outcome.

Methods: Records of 1802 patients with non-metastatic squamous cell HNC treated between 1998 and 2013 were retrospectively assessed from an institutional database. Patient demographics, tumor and treatment characteristics, and patient outcomes were abstracted from the chart. Differences between groups were assessed via logistic regression multivariate analysis (MVA). Outcomes including locoregional control (LRC) and overall survival (OS) were then estimated via Kaplan-Meier and Cox-regression MVA.

Results: Median follow up was 34 months. Patient races included white (n=1671, 93%), black (n=80, 4%), Asian (n=18, 1%), and other (n=33, 2%). On logistic regression MVA, Black patients were less likely to be married (39% vs. 63%; OR 0.5 95%CI 0.30-0.83, p=0.007) or be currently employed (43% vs. 61%; OR 0.44 95%CI 0.26-0.74, p=0.002) when compared to non-blacks. Black patients were also younger (54 vs. 59 years, p=0.001), more likely to present with advanced tumor stage (T4: 48% vs. 25%), and more often had >45days elapsed from diagnosis to treatment initiation (DTI) (61% vs. 49%, p=0.028). Delays in treatment, such as delayed diagnosis (advanced disease presentation) and delays in DTI>45days were also associated with marital and employment status. Black patients were associated with a lower 3-year LRC rate (65% vs. 81%, p<0.001) and OS rate (43% vs. 69%, p<0.001), compared to non-black patients. Patients with >45days DTI had a detriment in 3-year LRC (77% vs. 83%, p=0.002) and OS (66% vs. 69%, p=0.009). On Cox MVA, black race was independently prognostic for worse LRC (HR 1.62 95%CI 1.04-2.51, p=0.033) and OS (HR 1.55 95%CI 1.15-2.08, p=0.004) vs. non-blacks.

Conclusion: Black race is independently prognostic for LRC and OS. Delays in HNC treatment, such as more advanced tumor stage presentation and delays in treatment initiation, may be attributed to socioeconomic factors such as employment status and social support. Efforts to accommodate these factors may expedite treatment, in hopes of improving the race related outcome disparity in HNC.
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http://dx.doi.org/10.1016/j.canep.2016.09.005DOI Listing
December 2016