SMAD4 loss predicts worse overall and distant metastasis-free survival in patients with resected pancreatic adenocarcinoma.

BACKGROUND: In select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA-sequencing (RNA-seq) expression is a robust method for predicting overall survival (OS) and distant metastasis-free survival (DMFS) in patients with resected pancreatic adenocarcinoma. METHODS: Utilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I-III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA-seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA-seq via multivariable models and receiver operator characteristic curves. RESULTS: In TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00-2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87-2.03; p = .19). Low SMAD4 RNA-seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17-2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14-2.54; p = .009). In the ICGC, increased SMAD4 RNA-seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86-.94) and DMFS (AUC, .84; 95% CI, .82-.87). CONCLUSIONS: In patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA-seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA-seq expression may be a useful marker to predict metastatic spread.

Treatment Considerations for Patients with Locoregionally Advanced Head and Neck Cancer with a Contraindication to Cisplatin.

OPINION STATEMENT: Significant advancements have been made in the treatment of locally advanced head and neck cancer, predominantly driven by the integration of concurrent chemotherapy with radiation therapy as a standard of care for many patients. The most heavily investigated chemotherapeutic is cisplatin, yet many patients are ineligible for cisplatin due to the presence of pre-existing medical comorbidities. Moreover, given the toxicity profile of cisplatin, identifying which patients stand to benefit from cisplatin is challenging, which is particularly evident in older patients. Efforts to better risk-stratify patients based on age, performance status, and the degree of pre-existing comorbidities are ongoing and have been increasingly utilized in national clinical trials. In parallel, exploration into alternative systemic agents, including novel targeted therapies and immunotherapies, in cisplatin-ineligible patients are rapidly expanding. Cumulatively, identifying appropriate treatment paradigms in patients who harbor contraindications to cisplatin can not only improve clinical outcomes but also critically mitigate detrimental adverse effects.

Validation of NRG Oncology's prognostic nomograms for oropharyngeal cancer in the Veterans Affairs database.

BACKGROUND: To test whether nomograms developed by NRG Oncology for oropharyngeal squamous cell carcinoma (OPSCC) patients could be validated in an independent population-based sample. METHODS: The authors tested nomograms for estimating progression-free survival (PFS) and overall survival (OS) in patients from the Veterans Health Administration with previously untreated locoregionally advanced OPSCC, diagnosed between 2008 and 2017, managed with definitive radiotherapy with or without adjuvant systemic therapy. Covariates were age, performance status, p16 status, T/N category, smoking history, education history, weight loss, marital status, and anemia. We used multiple imputation to handle missing data and performed sensitivity analyses on complete cases. Validation was assessed via Cox proportional hazards models, log-rank tests, and c-indexes. RESULTS: A total of 4007 patients met inclusion criteria (658 patients had complete data). Median follow-up time was 3.20 years, with 967 progression events and 471 noncancer deaths. Each risk score was associated with poorer outcomes per unit increase (PFS score, hazard ratio [HR], 1.42 [1.37-1.47]; OS score, HR, 1.40 [1.34-1.45]). By risk score quartile, 2-year PFS estimates were 89.2%, 78.5%, 65.8%, and 48.3%; OS estimates were 92.6%, 83.6%, 73.9%, and 51.3%, respectively (P < .01 for all comparisons). C-indices for models of PFS and OS were 0.65 and 0.67, for all patients, respectively (0.69 and 0.73 for complete cases). The nomograms slightly overestimated PFS and OS in the overall cohort but exhibited high agreement in complete cases. CONCLUSIONS: NRG nomograms were effective for predicting PFS and OS for patients with OPSCC, supporting their broader applicability in the OPSCC population undergoing definitive radiotherapy.

NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Incomplete cisplatin regimens in chemoradiation and its effect on outcomes for locally advanced cervical cancer.

OBJECTIVE: To identify factors associated with receipt of incomplete cisplatin during chemoradiation for locally advanced cervical cancer and its impact on outcomes. METHODS: Patients with locally advanced cervical cancer treated with chemoradiation at our institution between November 2015 and August 2020 were retrospectively identified. Patients who received ≤4 cycles were identified as the 'incomplete' cohort and those who received 5-6 cycles as the 'complete' cohort. The primary endpoint of incomplete chemotherapy was evaluated with multivariable logistic regression. Secondary endpoints of locoregional failure, overall survival, and distant failure were evaluated in multivariable Cox and Fine-Gray models. RESULTS: Of 140 patients with locally advanced cervical cancer that underwent chemoradiation, 22 (15.7%) received an incomplete cisplatin regimen (8 with 0 cycles, 14 with 1-4 cycles). The most common reasons for receiving incomplete treatment were comorbidities/infections (41%), unmet laboratory parameters (27%), and cisplatin intolerance (14%). In multivariable models, only poor (2-4) Eastern Cooperative Oncology Group performance status was a significant predictor as these patients were 41 times more likely to receive incomplete chemotherapy (odds ratio (OR), 95% confidence interval (CI) 4.57 to 375.15, p<0.001). Median follow-up time was 20 months (range 4-64). In multivariable models, receipt of incomplete cisplatin was significantly associated with higher recurrence (locoregional failure hazard ratio (HR) 3.02, 95% CI 1.08 to 8.45, p=0.03; distant failure HR 2.71, 95% CI 1.13 to 6.47, p=0.02) and worse survival (overall survival HR 4.91, 95% CI 1.27 to 18.98, p=0.02). CONCLUSION: Incomplete cisplatin regimen was associated with worse oncologic outcomes. Poor performance status was the only factor associated with receiving an incomplete regimen. This notable proportion of patients may be a target for better tolerated novel targeted anticancer agents in order to improve outcomes.

Disparities in time to start of definitive radiation treatment for patients with locally advanced cervical cancer.

BACKGROUND: Chemoradiation or radiation therapy alone are curative standards for patients with locally advanced cervical cancer. OBJECTIVE: To investigate factors that influence time to initiation of chemoradiation or radiation and the subsequent impact of time to treatment on recurrence and survival outcomes. METHODS: Patients with locally advanced cervical cancer treated with definitive chemoradiation or radiation at our institution between November 2015 and August 2020 were retrospectively identified. Time to treatment initiation was defined as the number of days from date of diagnosis (via biopsy) to the start date of radiation. The cohort was stratified by the median time to treatment into early (<75 days) and delayed (≥75 days) cohorts. Multivariable logistic regression was conducted to examine factors associated with delayed time to treatment. RESULTS: We identified 143 patients with locally advanced cervical cancer who underwent definitive chemoradiation or radiation. Median follow-up time was 18 months (range 2-62). A total of 71 (49.7%) patients had time to treatment <75 days and 72 (50.3%) patients had time to treatment ≥75 days. The delayed cohort had a higher proportion of Hispanic patients (51.4% vs 31.0%, p=0.04). In multivariable modeling, Hispanic women were 2.71 times more likely (p=0.04) to undergo delayed time to treatment than non-Hispanic white women. Additionally, patients with stage >IIB disease were less likely to undergo delayed time to treatment (OR 0.26, p=0.02) than patients with stage

Imaging Biomarkers and Liquid Biopsy in Assessment of Cervical Cancer.

ABSTRACT: The role of imaging has been increasing in pretherapy planning and response assessment in cervical cancer, particularly in high-resource settings that provide access to computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). In 2018, imaging was incorporated into the International Federation of Gynecology and Obstetrics staging system for cervical cancer. Magnetic resonance imaging is advantageous over CT for evaluation of the primary cervical cancer size and extent, because of superior contrast resolution. Furthermore, quantitative methods, including diffusion-weighted and dynamic contrast-enhanced MRI, show promise in improving treatment response and prognosis evaluation. Molecular imaging with fluorodeoxyglucose-PET/CT and PET/MRI can be particularly helpful in the detection of nodal disease and distant metastases. Semiautomated delineation of 3-dimensional tumor regions of interest has facilitated the development of novel PET-derived biomarkers that include metabolic volume and radiomics textural analysis features for prediction of outcomes. However, posttreatment inflammatory changes can be a confounder and lymph node evaluation is challenging, even with the use of PET/CT. Liquid biopsy has emerged as a promising tool that may be able to overcome some of the drawbacks inherent with imaging, such as limited ability to detect microscopic metastases or to distinguish between postchemoradiotherapy changes and residual tumor. Preliminary evidence suggests that liquid biopsy may be able to identify cervical cancer treatment response and resistance earlier than traditional methods. Future work should prioritize how to best synergize imaging and liquid biopsy as an integrated approach for optimal cervical cancer management.

Validation of an oncology-specific opioid risk calculator in cancer survivors.

BACKGROUND: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors. METHODS: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves. RESULTS: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2 years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869. CONCLUSIONS: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes. LAY SUMMARY: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy.

Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety.

Radiation therapy exerts a tumoricidal local effect as well as both local and systemic immunomodulation. Immune checkpoint blockade has become a widely used treatment modality across cancer types with a rapidly growing list of agents and US Food and Drug Administration-approved indications. Moreover, there may be synergy between radiation therapy and immune checkpoint blockade. Various strategies have been used, but the optimal sequencing of these therapies is unclear. In this review, the authors discuss the major mechanisms of available immune checkpoint inhibitors and explore the available preclinical and clinical evidence regarding treatment sequencing. They also review safety considerations and conclude with possible future directions.

Predictive classifier for intensive treatment of head and neck cancer.

BACKGROUND: This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer. METHODS: This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS). RESULTS: Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011). CONCLUSIONS: LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.

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

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.

Undertreatment of women with locoregionally advanced head and neck cancer.

BACKGROUND: It is difficult to predict whether a patient with head and neck cancer (HNC) is more likely to die of the cancer or another comorbidity. Competing event models can help to identify individual patients or groups of patients who may be undertreated or overtreated in clinical practice. METHODS: Patients with HNC (n = 884), aged 18 to 85 years and diagnosed from 2000 to 2015 with stage II to IVB disease according to the seventh edition of the American Joint Committee on Cancer system, were identified. With a generalized competing event (GCE) model that controlled for age, sex, tumor site, surgical treatment, and Charlson Comorbidity Index (CCI), the association between these factors and the relative hazard for cancer mortality was determined. Logistic regression models were used to estimate the odds of receiving platinum-based chemoradiotherapy or a less intensive therapy, with adjustments made for age, sex, tumor site, CCI, stage, smoking, and alcohol abuse history. RESULTS: Compared with men, women had an increased relative hazard ratio for death from HNC versus other causes, which was reported as an adjusted ω+ ratio comparing women with men (ω+ ratio, 1.95; 95% CI, 1.09-3.49), even though they were less likely to receive intensive chemoradiotherapy than men (adjusted odds ratio, 0.69; 95% CI, 0.48-0.99). CONCLUSIONS: These findings indicate that women in this cohort may be undertreated in clinical practice and potentially miss the opportunity for their HNC to be aggressively treated. This study supports the use of GCE models to identify patients who are potentially undertreated and may also help to guide future research in health disparities.

The Impact of Surgeons on the Likelihood of Mastectomy in Breast Cancer.

OBJECTIVE: This study evaluates the impact of individual surgeons and institutions on the use of mastectomy or breast conserving surgery (BCS) among elderly women with breast cancer. SUMMARY OF BACKGROUND DATA: Current literature characterizes patient clinical and demographic factors that increase likelihood of mastectomy use. However, the impact of the individual provider or institution is not well understood, and could provide key insights to biases in the decision-making process. METHODS: A retrospective cohort study of 29,358 women 65 years or older derived from the SEER-Medicare linked database with localized breast cancer diagnosed from 2000 to 2009. Multilevel, multivariable logistic models were employed, with odds ratios (ORs) used to describe the impact of demographic or clinical covariates, and the median OR (MOR) used to describe the relative impact of the surgeon and institution. RESULTS: Six thousand five hundred ninety-four women (22.4%) underwent mastectomy. Unadjusted rates of mastectomy ranged from 0% in the bottom quintile of surgeons to 58.0% in the top quintile. On multivariable analysis, the individual surgeon (MOR 1.97) had a greater impact on mastectomy than did the institution (MOR 1.71) or all other clinical and demographic variables except tumor size (OR 3.06) and nodal status (OR 2.95). Surgeons with more years in practice, or those with a lower case volume were more likely to perform mastectomy (P < 0.05). CONCLUSION: The individual surgeon influences the likelihood of mastectomy for the treatment of localized breast cancer. Further research should focus on physician-related biases that influence this decision to ensure patient autonomy.

'Optimism bias' in contemporary national clinical trial network phase III trials: are we improving?

Background: Previous studies have found that overestimating treatment effects (i.e. 'optimism bias') leads to underpowered clinical trials. The prevalence of 'optimism bias' in contemporary National Clinical Trials Network (NCTN) cancer clinical trials is unknown. Methods: We conducted a systematic review of NCTN phase III randomized trials published from January 2007 to January 2017. We compared the hypothesized versus observed treatment effects in each trial, and examined whether trial-related factors were correlated with the study results. We also reviewed the methods of each protocol to assess whether a rationale for the hypothesized effect size was provided. Results: We identified 161 clinical trials, of which 130 were eligible for analysis. Original protocols could not be located for 8 trials (5.0%). Twenty-eight trials (21.5%) observed a statistically significant difference in the primary end point favoring the experimental treatment. The median ratio of observed-to-expected hazard ratios among trials that observed a statistically significant effect on the primary end point was 1.07 (range: 0.33-1.28) versus 1.32 (range: 0.86-2.02) for trials that did not, compared with 1.34 and 1.86, respectively, for National Cancer Institute (NCI) trials published between 1955 and 2006. An effect size at least as large as the one projected in the protocol trials was observed in 9.8% of trials, compared with 17% of NCI trials published from 1955 to 2006. Most trials (64.6%) provided no rationale to support the magnitude of the proposed treatment effect in the protocol. Conclusions: Despite a reduction in 'optimism bias' compared with previous eras, most contemporary NCTN phase III trials failed to establish statistically significant benefits of new cancer therapies. Better rationalization of proposed effect sizes in research protocols is needed.

Underutilization of brachytherapy and disparities in survival for patients with cervical cancer in California.

PURPOSE: The treatment for locally advanced cervical cancer is external beam radiation (EBRT), concurrent chemotherapy, and brachytherapy (BT). We investigated demographic and socioeconomic factors that influence trends in BT utilization and disparities in survival. METHODS: Using the California Cancer Registry, cervical cancer patients FIGO IB2-IVA from 2004 to 2014 were identified. We collected tumor, demographic and socioeconomic (SES) factors. We used multivariable logistic regression analysis to determine predictors of use of BT. Using Cox proportional hazards, we examined the impact of BT vs EBRT boost on cause specific (CSS) and overall survival (OS). RESULTS: We identified 4783 patients with FIGO stage 11% IB2; 32% II, 54% III, 3% IVA. Nearly half (45%) of patients were treated with BT, 18% were treated with a EBRT boost, and 37% had no boost. Stage II and III were more likely to be treated with BT (p = 0.002 and p = 0.0168) vs Stage IB2. As patients aged, the use of BT decreased. Using multivariate analysis, BT impacted CCS (HR 1.16, p = 0.0330) and OS (HR 1.14, p = 0.0333). Worse CSS was observed for black patients (p = 0.0002), low SES (p = 0.0263), stage III and IVA (p < 0.0001. Black patients, low and middle SES had worse OS, (p = 0.0003). CONCLUSIONS: The utilization of BT in locally advanced cervical cancer was low at 45%, with a decrease in CSS and OS. Black patients and those in low SES had worse CSS. As we strive for outcome improvement in cervical cancer, we need to target increasing access and disparities for quality and value.

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

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.

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

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.

Patterns of Palliative Care Consultation Among Elderly Patients With Cancer.

BACKGROUND: The role of palliative care has expanded over the past several decades, although the oncology-specific regional evolution of this specialty has not been characterized at the population-based level. METHODS: This study defined the patterns of palliative care delivery using a retrospective cohort of patients with advanced cancer within the SEER-Medicare linked database. We identified 83,022 patients with metastatic breast, prostate, lung, and colorectal cancers. We studied trends between 2000 through 2009, and determined patient-level and regional-level predictors of palliative care delivery. RESULTS: Palliative care consultation rates increased from 3.0% in 2000 to 12.9% in 2009, with most consultations occurring in the last 4 weeks of life (77%) in the inpatient hospital setting. The rates of palliative care delivery were highest in the West (7.6%) and lowest in the South (3.2%). The likelihood of palliative care consultation increased with decreasing numbers of regional acute care hospital beds per capita. The use of palliative care consultation increased with increasing numbers of regional physicians. The use of palliative care decreased with increasing regional Medicare expenditure with a $1,387 difference per beneficiary between the first and fourth quartiles of palliative care use. CONCLUSIONS: Geographic location influences a patient's options for palliative care in the United States. Although the overall rates of palliative care are increasing, future effort should focus on improving palliative care services in regions with the least access.

Aspiration pneumonia after concurrent chemoradiotherapy for head and neck cancer.

BACKGROUND: Aspiration pneumonia represents an under-reported complication of chemoradiotherapy in patient with head and neck cancer. The objective of the current study was to evaluate the incidence, risk factors, and mortality of aspiration pneumonia in a large cohort of patients with head and neck cancer who received concurrent chemoradiotherapy. METHODS: Patients who had head and neck cancer diagnosed between 2000 and 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Aspiration pneumonia was identified from Medicare billing claims. The cumulative incidence, risk factors, and survival after aspiration pneumonia were estimated and compared with a noncancer population. RESULTS: Of 3513 patients with head and neck cancer, 801 developed aspiration pneumonia at a median of 5 months after initiating treatment. The 1-year and 5-year cumulative incidence of aspiration pneumonia was 15.8% and 23.8%, respectively, for patients with head and neck cancer and 3.6% and 8.7%, respectively, for noncancer controls. Among the patients with cancer, multivariate analysis identified independent risk factors (P < .05) for aspiration pneumonia, including hypopharyngeal and nasopharyngeal tumors, male gender, older age, increased comorbidity, no surgery before radiation, and care received at a teaching hospital. Among the patients with cancer who experienced aspiration pneumonia, 674 (84%) were hospitalized; and, of these, 301 (45%) were admitted to an intensive care unit. The 30-day mortality rate after hospitalization for aspiration pneumonia was 32.5%. Aspiration pneumonia was associated with a 42% increased risk of death (hazard ratio, 1.42; P < .001) after controlling for confounders. CONCLUSIONS: The current results indicated that nearly 25% of elderly patients will develop aspiration pneumonia within 5 years after receiving chemoradiotherapy for head and neck cancer. A better understanding of mitigating factors will help identify patients who are at risk for this potentially lethal complication.

Angiotensin-converting enzyme inhibitors predict acute kidney injury during chemoradiation for head and neck cancer.

Head and neck cancer patients undergoing chemoradiation experience considerable toxicities including acute kidney injury (AKI). However, it remains unclear what factors predispose patients to renal toxicity during treatment. Here, we assessed the predictors and outcomes of patients experiencing AKI during chemoradiation. We carried out a retrospective cohort study to assess the maximum changes in serum creatinine (Cr) in 173 patients with stage III-IV head and neck cancer treated with chemoradiation between 1999 and 2012. We defined AKI as Cr increases 26.5 µmol/l or more over the pretreatment baseline. AKI was associated with angiotensin-converting enzyme inhibitor (ACEI) use (33.0 vs. 11.0%; P=0.0004), but no other medications or comorbidities. On multivariate analysis, ACEI use, weight loss 10% or more of body weight, and performance status 70 or more predicted for Cr increments 26.5 µmol/l or more, whereas only ACEI use predicted for Cr increments of 44.2 µmol/l or greater. Furthermore, on multivariate analysis, AKI predicted for more interventions during radiotherapy including intravenous fluid use (P=0.0005) and hospitalizations (P=0.007), as well as long-term renal dysfunction (P<0.0001). Renal toxicity was not associated with worse locoregional control, progression-free survival, or overall survival. Renal toxicity during chemoradiation was associated with ACEI use alone or coupled with weight loss 10% or more of body weight during therapy. Our results suggest that actively managing ACEI use and intravascular volume status during chemoradiation may avoid AKI, minimize subsequent interventions, and reduce the risk for long-term renal dysfunction.