Substance use and mental health burden in head and neck and other cancer survivors: A National Health Interview Survey analysis.

BACKGROUND: Tobacco dependence, alcohol abuse, depression, distress, and other adverse patient-level influences are common in head and neck cancer (HNC) survivors. Their interrelatedness and precise burden in comparison with survivors of other cancers are poorly understood. METHODS: National Health Interview Survey data from 1997 to 2016 were pooled. The prevalence of adverse patient-level influences among HNC survivors and matched survivors of other cancers were compared using descriptive statistics. Multivariable logistic regressions evaluating covariate associations with the primary study outcomes were performed. These included 1) current cigarette smoking and/or heavy alcohol use (>14 drinks per week) and 2) high mental health burden (severe psychological distress [Kessler Index ≥ 13] and/or frequent depressive/anxiety symptoms). RESULTS: In all, 918 HNC survivors and 3672 matched survivors of other cancers were identified. Compared with other cancer survivors, more HNC survivors were current smokers and/or heavy drinkers (24.6% [95% CI, 21.5%-27.7%] vs 18.0% [95% CI, 16.6%-19.4%]) and exhibited a high mental health burden (18.6% [95% CI, 15.7%-21.5%] vs 13.0% [95% CI, 11.7%-14.3%]). In multivariable analyses, 1) a high mental health burden predicted for smoking and/or heavy drinking (odds ratio [OR], 1.4; 95% CI, 1.0-1.9), and 2) current cigarette smoking predicted for a high mental health burden (OR, 1.7; 95% CI, 1.2-2.3). Furthermore, nonpartnered marital status and uninsured/Medicaid insurance status were significantly associated with both cigarette smoking and/or heavy alcohol use (ORs, 1.9 [95% CI, 1.4-2.5] and 1.5 [95% CI, 1.0-2.1], respectively) and a high mental health burden (ORs, 1.4 [95% CI, 1.1 -1.8] and 3.0 [95% CI, 2.2-4.2], respectively). CONCLUSIONS: Stakeholders should allocate greater supportive care resources to HNC survivors. The interdependence of substance abuse, adverse mental health symptoms, and other adverse patient-level influences requires development of novel, multimodal survivorship care interventions.

Long-term opioid use in patients treated with head and neck intensity-modulated radiotherapy.

PURPOSE: Acute and chronic pain during and after radiotherapy is an important driver of poor quality of life. We aimed to identify risk factors associated with increased chronic opioid use in head and neck squamous cell cancer survivors. METHODS: We performed a retrospective cohort analysis on head and neck squamous cell cancer patients treated with definitive or adjuvant intensity-modulated radiotherapy. We tracked their oncologic opioid prescription profile from initial presentation to the last follow-up date. We determined the incidences of 1- and 2-year opioid use and performed multivariate logistic regression for both outcomes. RESULTS: Our analytic cohort consisted of 403 head and neck squamous cell cancer survivors. The numbers of patients requiring opioids at 3 months, 6 months, and 1 year after treatment were 316 (78%), 203 (50%), and 102 (25%), respectively. On multivariate logistic regression, positive smoking history (95% CI 1.86 [1.03, 3.43], p = 0.04), unemployment (95% CI 2.33 [1.16, 4.67], p = 0.02), prior psychiatric illness (95% CI 2.15 [1.05, 4.40], p = 0.03), and opiate use before radiotherapy (95% CI 2.75 [1.49, 5.20], p = 0.01) were independently associated with significantly greater odds of opioid use at 1 year. CONCLUSIONS: Our institutional analysis has shown that a substantial amount of head and neck cancer survivors are chronically dependent on opioids following radiotherapy. We have identified a cohort at highest risk for long-term use, for whom early interventions should be targeted.

Smoking and other patient factors in HPV-mediated oropharynx cancer: A retrospective cohort study.

PURPOSE: To characterize the significance of patient-level influences, including smoking history, on oncologic outcomes in human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC). MATERIALS AND METHODS: A bi-institutional retrospective cohort study of previously untreated, HPV+ OPC patients who underwent curative treatment from 1/1/2008 to 7/1/2018 was performed. The primary outcome was disease-free survival (DFS) and the primary exposure was ≤10 versus >10-pack-year (PY)-smoking history. RESULTS: Among 953 OPC patients identified, 342 individuals with HPV+ OPC were included. The median patient age was 62 years, 33.0% had a > 10-PY-smoking history, 60.2% had AJCC8 stage I disease, and 35.0% underwent primary surgery. The median follow-up was 49 months (interquartile range [IQR] 32-75 months). Four-year DFS-estimates were similar among patients with ≤10-PY-smoking history (78.0%, 95% CI:71.7%-83.1%) compared to >10-PYs (74.8%; 95% CI:65.2%-82.0%; log-rank:p = 0.53). On univariate analysis, >10-PY-smoking history did not correlate with DFS (hazard ratio[HR]:1.15;95% CI:0.74-1.79) and remained nonsignificant when forced into the multivariable model. On adjusted analyses, stage, treatment paradigm, and age predicted DFS. Neither >10-PYs, nor any other definition of tobacco use (e.g., current smoker or > 20-PYs) was predictive of DFS, overall survival, or disease-specific survival. Conversely, age nonsignificantly and significantly predicted adjusted DFS (adjusted HR[aHR]:1.02,95% CI:0.997-1.05, p = 0.08), overall survival (aHR 1.05; 95% CI: 1.02-1.08; p = 0.002) and disease-specific survival (aHR 1.04;95% CI: 0.99-1.09;p = 0.09). CONCLUSION: Other than age, patient-level influences may not be primary drivers of HPV+ OPC outcomes. Although limited by its modest sample size, our study suggests the significance of smoking has been overstated in this disease. These findings and the emerging literature collectively do not support risk-stratification employing the >10-PY threshold. LEVEL OF EVIDENCE: Level 4.

High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Clinical Review.

BACKGROUND: Given the rapidly evolving nature of the field, the current state of "high-risk" head and neck cutaneous squamous cell carcinoma (HNcSCC) is poorly characterized. METHODS: Narrative review of the epidemiology, diagnosis, workup, risk stratification, staging and treatment of high-risk HNcSCC. RESULTS: Clinical and pathologic risk factors for adverse HNcSCC outcomes are nuanced (e.g., immunosuppression and perineural invasion). Frequent changes in adverse prognosticators have outpaced population-based registries and the variables they track, restricting our understanding of the epidemiology of HNcSCC and inhibiting control of the disease. Current heterogeneous staging and risk stratification systems are largely derived from institutional data, compromising their external validity. In the absence of staging system consensus, tumor designations such as "high risk" and "advanced" are variably used and insufficiently precise to guide management. Evidence guiding treatment of high-risk HNcSCC with curative intent is also suboptimal. For patients with incurable disease, an array of trials are evaluating the impact of immunotherapy, targeted biologic therapy, and other novel agents. CONCLUSION: Population-based registries that broadly track updated, nuanced, adverse clinicopathologic risk factors, and outcomes are needed to guide development of improved staging systems. Design and development of randomized controlled trials (RCTs) in advanced-stage HNcSCC populations are needed to evaluate (1) observation, sentinel lymph node biopsy, or elective neck dissection for management of the cN0 neck, (2) indications for surgery plus adjuvant radiation versus adjuvant chemoradiation, and (3) the role of immunotherapy in treatment with curative intent. Considering these knowledge gaps, the authors explore a potential high-risk HNcSCC treatment framework.

Alcohol Use Among Patients With Cancer and Survivors in the United States, 2000-2017.

BACKGROUND: Alcohol use is an established risk factor for several malignancies and is associated with adverse oncologic outcomes among individuals diagnosed with cancer. The prevalence and patterns of alcohol use among cancer survivors are poorly described. METHODS: We used the National Health Interview Survey from 2000 to 2017 to examine alcohol drinking prevalence and patterns among adults reporting a cancer diagnosis. Multivariable logistic regression was used to define the association between demographic and socioeconomic variables and odds of self-reporting as a current drinker, exceeding moderate drinking limits, and engaging in binge drinking. The association between specific cancer type and odds of drinking were assessed. RESULTS: Among 34,080 survey participants with a known cancer diagnosis, 56.5% self-reported as current drinkers, including 34.9% who exceeded moderate drinking limits and 21.0% who engaged in binge drinking. Younger age, smoking history, and more recent survey period were associated with higher odds of current, exceeding moderate, and binge drinking (P<.001 for all, except P=.008 for excess drinking). Similar associations persisted when the cohort was limited to 20,828 cancer survivors diagnosed ≥5 years before survey administration. Diagnoses of melanoma and cervical, head and neck, and testicular cancers were associated with higher odds of binge drinking (P<.05 for all) compared with other cancer diagnoses. CONCLUSIONS: Most cancer survivors self-report as current alcohol drinkers, including a subset who seem to engage in excessive drinking behaviors. Given that alcohol intake has implications for cancer prevention and is a potentially modifiable risk factor for cancer-specific outcomes, the high prevalence of alcohol use among cancer survivors highlights the need for public health strategies aimed at the reduction of alcohol consumption.

Prevalence of chronic pain among cancer survivors in the United States, 2010-2017.

BACKGROUND: There are a growing number of cancer survivors in the United States who are at risk for chronic pain due to cancer disease and treatments. The prevalence of chronic pain among cancer survivors has not been comprehensively reported. METHODS: This study used data from the National Health Interview Survey (2010-2017) to compare the prevalence of chronic pain between participants with a cancer diagnosis and participants without one. Adjusted odds ratios (AORs) of having chronic pain were assessed by multivariable logistic regression, which included an age (less than the median age vs greater than or equal to the median age) × cancer diagnosis (yes vs no) interaction term. Among cancer survivors, multivariable logistic regression defined the odds of feeling depressed, feeling worried/nervous/anxious, being unable to work, and needing assistance for activities of daily living (ADLs) and instrumental activities of daily living (IADLs). RESULTS: Among 115,091 participants, a cancer diagnosis was associated with an increased AOR of chronic pain in comparison with the general population (30.8% vs 15.7%; AOR, 1.48; 95% confidence interval, 1.38-1.59). Older age was associated with higher odds of chronic pain (P < .001 across all increasing age categories); however, the positive association between older age and chronic pain was seen only in participants without cancer and was not seen in those with a cancer diagnosis (Page×cancer  < .001). Among patients reporting a cancer diagnosis, chronic pain was associated with greater odds of feeling depressed, feeling worried/nervous/anxious, being unable to work, and needing assistance with ADLs or IADLs (P < .001 for all). CONCLUSIONS: Cancer survivors appear to have a high prevalence of chronic pain, which is associated with worse mental, functional, and employment outcomes. Screening and management of chronic pain should be addressed by policymakers to improve cancer survivorship care.

Sociodemographic Disparities in the Receipt of Adjuvant Chemotherapy Among Patients With Resected Stage I-III Pancreatic Adenocarcinoma.

BACKGROUND: Adjuvant therapy for resected pancreatic adenocarcinoma was given a category 1 NCCN recommendation in 2000, yet many patients do not receive chemotherapy after definitive surgery. Whether sociodemographic disparities exist for receipt of adjuvant chemotherapy is poorly understood. METHODS: The National Cancer Database was used to identify patients diagnosed with nonmetastatic pancreatic adenocarcinoma who underwent definitive surgery from 2004 through 2015. Multivariable logistic regression defined the adjusted odds ratio (aOR) and associated 95% CI of receipt of adjuvant chemotherapy. Among patients receiving chemotherapy, multivariable logistic regression assessed the odds of treatment with multiagent chemotherapy. RESULTS: Among 18,463 patients, 11,288 (61.1%) received any adjuvant chemotherapy. Sociodemographic factors inversely associated with receipt of any adjuvant chemotherapy included uninsured status (aOR, 0.61; 95% CI, 0.50-0.74), Medicaid insurance (aOR, 0.66; 95% CI, 0.57-0.77), and lower income (P<.001 for all income levels compared with ≥$46,000). Black race (aOR, 0.72; 95% CI, 0.57-0.90) and female sex (aOR, 0.75; 95% CI, 0.65-0.86) were associated with lower odds of receiving multiagent chemotherapy. There was a statistically significant interaction term between black race and age/comorbidity status (P=.03), such that 26.4% of black versus 35.8% of nonblack young (aged ≤65 years) and healthy (Charlson-Deyo comorbidity score 0) patients received multiagent adjuvant chemotherapy (P=.006), whereas multiagent adjuvant chemotherapy rates were similar among patients who were not young and healthy (P=.15). CONCLUSIONS: In this nationally representative study, receipt of adjuvant chemotherapy appeared to be associated with sociodemographic characteristics, independent of clinical factors. Sociodemographic differences in receipt of adjuvant chemotherapy may represent a missed opportunity for improving outcomes and a driver of oncologic disparities.

Malignant Peritoneal Mesothelioma: National Practice Patterns, Outcomes, and Predictors of Survival.

PURPOSE: This study of a large, contemporary national database evaluated management patterns, outcomes, and prognostic factors of malignant peritoneal mesothelioma (MPM) in the USA. METHODS: The National Cancer Data Base was queried for newly diagnosed nonmetastatic MPM. Patients were divided into five cohorts: observation, chemotherapy alone, cytoreductive surgery (CRS) alone, CRS/chemo [referring to any non-hyperthermic intraperitoneal chemotherapy (HIPEC) chemotherapy], and CRS/HIPEC. Statistics included multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards modeling. RESULTS: Of 1514 patients, 379 (25%) underwent observation, 370 (24%) received chemotherapy only, 197 (13%) CRS alone, 352 (23%) CRS/chemo, and 216 (14%) CRS/HIPEC. No major temporal trends in management were noted. Factors predictive of CRS administration included younger age, female gender, insurance status, residence in educated areas, living farther from treating institutions, and treatment at academic centers (p < 0.05 for all). Compared with epithelioid histology, those with sarcomatoid and biphasic histology were less and more likely to undergo CRS, respectively (p < 0.05 for both). In all CRS patients, 30- and 90-day mortality rates were 0.8 and 1.2%, respectively. At median follow-up of 50 months, median OS in the respective groups was 6, 17, 21, 52, and 61 months (p < 0.001). Poor prognostic factors included advanced age, male gender, uninsured/Medicaid insurance, and sarcomatoid/biphasic histology (p < 0.05 for all). CONCLUSIONS: In the USA, MPM is treated using a wide variety of strategies. Many factors impact the type of treatment delivered, including age, sociodemographics, geography, histology, and facility type. Although these data do not imply causation, combined-modality management seems associated with the longest OS.

National patterns of care and predictors of neoadjuvant and concurrent chemotherapy use with definitive radiotherapy in the treatment of patients with oropharyngeal squamous cell carcinoma.

BACKGROUND: To the authors' knowledge, the patterns of care for the radiotherapy-based treatment of patients with stage III to IVB oropharyngeal squamous cell carcinoma (OPSCC) are poorly defined. The objective of the current study was to characterize the use and predictors of chemotherapy with radiotherapy for this population using the National Cancer Database. METHODS: Patients in the National Cancer Database with AJCC (American Joint Committee on Cancer) stage III to IV OPSCC who were treated with radiotherapy between 2003 and 2012 were eligible for analysis. Treatment was defined as radiotherapy alone, concurrent chemoradiotherapy, or induction chemotherapy (IC). Multivariable regression with multilevel modeling was used to determine predictors of any chemotherapy use and, among patients receiving chemotherapy, the predictors of IC. RESULTS: The majority (90%) of the 30,875 eligible patients received chemotherapy, the majority of whom (71% of the total) were treated with definitive chemoradiotherapy; a sizeable percentage of patients received IC (19% of total). On multivariable regression, younger age, favorable comorbidity status, and more advanced tumor and lymph node disease were found to be independent predictors of any chemotherapy and IC use. Nonwhite patients (odds ratio [OR], 0.71; P<.0001), women (OR, 0.74; P<.0001), and individuals without private insurance were found to be significantly less likely to receive chemotherapy. Patients treated at higher-volume institutions were significantly less likely to receive IC (OR, 0.69; P = .0006). Human papillomavirus status did not appear to independently influence treatment choice. CONCLUSIONS: The vast majority of patients with stage III to IVB OPSCC who were treated with definitive radiotherapy received chemotherapy, which is consistent with high-level data and national recommendations. However, disparities with regard to race, sex, and insurance status emerged thereby requiring additional investigation. The frequent use of IC despite limited supportive evidence warrants research on physician and patient decision making and presents an opportunity to improve evidence-based treatment delivery. Cancer 2017;123:273-282. © 2016 American Cancer Society.

Adjuvant radiotherapy improves overall survival in patients with resected gastric adenocarcinoma: A National Cancer Data Base analysis.

BACKGROUND: For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens. METHODS: Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed. RESULTS: A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001). CONCLUSIONS: In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017;123:3402-9. © 2017 American Cancer Society.

Association between hospital volume and receipt of treatment and survival in patients with glioblastoma.

The relation between hospital volume and outcomes for patients with glioblastoma is unknown. We undertook this study to determine the effect of hospital volume on treatment received and its effect on survival in patients with glioblastoma. We included patients from the National Cancer Database diagnosed with a glioblastoma from 2006 to 2013. Hospital volume was calculated by examining the treating facilities average number of cases per year and grouping them into tertiles: (low < 9.25, medium 9.26-23.88, and high ≥ 23.39). Treatment was defined as receiving any type of therapeutic surgery, radiation or chemotherapy. Using regression models we examined the relation between hospital volume to treatment received and survival with adjustment for clinical, socioeconomic and institutional factors. The study included 68,726 patients of which 91.8% received treatment. Among patients diagnosed at low volume facilities, 90.1% received treatment versus 94.2% in high volume facilities (p < 0.0001). Compared to low volume centers, the odds ratio of receiving any treatment was 1.01 (CI 95% CI: 0.95-1.09) and 1.43 (95% CI: 1.31-1.55) for medium volume and high volume facilities, respectively. On multivariate analysis for survival among those who received treatment, the hazard of mortality was decreased at high volume (HR 0.92, 95% CI 0.89-0.94) facilities compared to low volume facilities. Patients diagnosed with glioblastoma at a high volume facility (≥23.39 cases per year) have an increased likelihood of receiving treatment. Furthermore, glioblastoma patients may significantly improve their survival by choosing to receive care at a high-volume hospital.

Cost-Effectiveness of Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: a Critical Review.

PURPOSE OF REVIEW: This review aims to summarize and appraise published cost-effectiveness studies on stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). RECENT FINDINGS: We performed a Medline search of cost-effectiveness studies of SRS, SBRT, and other cancer treatment modalities such as surgery and systemic therapy from 2006 to 2016. We included studies that used both modeling and retrospective review techniques. We excluded studies of benign disease. We defined a strategy whose incremental cost-effectiveness ratio (ICER) is ≤$50,000/quality-adjusted life year (QALY) as "clearly cost-effective," a strategy whose ICER is ≤$100,000/QALY as "probably cost-effective," and a strategy ≤$200,000/QALY as "possibly cost-effective." We appraised modeling studies by determining whether or not they conform to the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices (ISPOR) in modeling task force good research practices in model transparency and validation. We identified 24 studies that met inclusion criteria. Treatment sites included brain, bone, liver, lung, pancreas, and prostate. SRS and SBRT were clearly cost-effective strategies in 17 studies, probably cost-effective in 3 studies, and possibly cost-effective in 2 studies. Of the 16 modeling studies,15 conformed to transparency best practices; however, only 6 studies performed rigorous validation as described by the ISPOR guidelines. CONCLUSIONS: SRS and SBRT are likely to be cost-effective management strategies across a large variety of treatment sites and techniques. However, rigorous model validation techniques are lacking in these modeling studies.

Cost-effectiveness analysis of neurocognitive-sparing treatments for brain metastases.

BACKGROUND: Decisions regarding how to treat patients who have 1 to 3 brain metastases require important tradeoffs between controlling recurrences, side effects, and costs. In this analysis, the authors compared novel treatments versus usual care to determine the incremental cost-effectiveness ratio from a payer's (Medicare) perspective. METHODS: Cost-effectiveness was evaluated using a microsimulation of a Markov model for 60 one-month cycles. The model used 4 simulated cohorts of patients aged 65 years with 1 to 3 brain metastases. The 4 cohorts had a median survival of 3, 6, 12, and 24 months to test the sensitivity of the model to different prognoses. The treatment alternatives evaluated included stereotactic radiosurgery (SRS) with 3 variants of salvage after recurrence (whole-brain radiotherapy [WBRT], hippocampal avoidance WBRT [HA-WBRT], SRS plus WBRT, and SRS plus HA-WBRT). The findings were tested for robustness using probabilistic and deterministic sensitivity analyses. RESULTS: Traditional radiation therapies remained cost-effective for patients in the 3-month and 6-month cohorts. In the cohorts with longer median survival, HA-WBRT and SRS plus HA-WBRT became cost-effective relative to traditional treatments. When the treatments that involved HA-WBRT were excluded, either SRS alone or SRS plus WBRT was cost-effective relative to WBRT alone. The deterministic and probabilistic sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: HA-WBRT and SRS plus HA-WBRT were cost-effective for 2 of the 4 cohorts, demonstrating the value of controlling late brain toxicity with this novel therapy. Cost-effectiveness depended on patient life expectancy. SRS was cost-effective in the cohorts with short prognoses (3 and 6 months), whereas HA-WBRT and SRS plus HA-WBRT were cost-effective in the cohorts with longer prognoses (12 and 24 months).

Influence of conformal radiotherapy technique on survival after chemoradiotherapy for patients with stage III non-small cell lung cancer in the National Cancer Data Base.

BACKGROUND: Definitive chemoradiotherapy is a core treatment modality for patients with stage III non-small cell lung cancer (NSCLC). Although radiotherapy (RT) technologies have advanced dramatically, to the authors' knowledge relatively little is known regarding the importance of irradiation technique on outcome, particularly given the competing risk of distant metastasis. The National Cancer Data Base was used to determine predictors of overall survival (OS) in patients with AJCC stage III NSCLC who were treated with chemoradiotherapy, focusing on the importance of conformal RT (CRT). METHODS: Patients with stage III NSCLC who were treated with chemoradiotherapy between 2003 and 2005 in the National Cancer Data Base were included. RT technique was defined as conventional, 3-dimensional-conformal, or intensity-modulated RT (IMRT), the latter 2 combined as CRT. Cox proportional hazards regression was performed for univariable and multivariable analyses of OS. RESULTS: The median, 3-year, and 5-year survival outcomes for the 13,292 patients were 12.9 months, 19%, and 11%, respectively. The 3-year and 5-year survival probabilities of patients receiving CRT versus no CRT were 22% versus 19% and 14% versus 11%, respectively (P < .0001). On multivariable analysis, CRT was found to be significantly associated with improved OS (hazards ratio, 0.89). This effect was confirmed on sensitivity analyses, including restricting the cohort to minimum 6-month survivors, young patients with stage IIIA disease, and propensity score-matching. Institutional academic status and patient volume were not found to be associated with OS. CONCLUSIONS: CRT was found to be independently associated with a survival advantage. These results reflect the importance of optimal locoregional therapy in patients with stage III NSCLC and provide motivation for further study of advanced RT technologies in patients with NSCLC.

Target Delineation in Postoperative Radiation Therapy for Head and Neck Cancer After Flap Reconstruction.

Delineation of the clinical target volume (CTV) after resection of head and neck cancer can be challenging, especially after flap reconstruction. The main area of contention is whether the entire flap should be included in the CTV. Several case series have reported marginal misses and intraflap failures when the entire flap was not routinely included in the CTV. On the other hand, available data have not convincingly demonstrated a detriment to long-term outcomes using intensity modulated radiotherapy after flap reconstruction. On the contrary, postoperative radiation can facilitate epilation and mucosalization of the flap tissue, reduce flap bulk, and improve long-term esthetic and functional outcomes. Therefore, our standard practice is to include the entire flap in the CTV. In certain scenarios, we may allow for a lower dose to part of flap distant from the resection bed than the flap-tumor bed junction, where recurrences are most likely. We provide three case vignettes describing such scenarios where sparing part of the flap, and more importantly, the nearby uninvolved native tissue, from high-dose radiation may be justified.

Death from high-risk prostate cancer versus cardiovascular mortality with hormonal therapy: a decision analysis.

BACKGROUND: Randomized trials have demonstrated improved survival when hormonal therapy (HT) is added to radiation therapy (RT) for high-risk prostate cancer. However, it is still unknown whether men who have a history of myocardial infarction (MI) or MI risk factors achieve a superior outcome from HT. METHODS: A Markov decision analysis model was used to compare quality-adjusted life expectancy (QALE) in men aged 50, 60, and 70 years who received RT and no HT, 6 months of HT (short-term), or 3 years of HT (long-term) for high-risk prostate cancer stratified by cardiac risk group. RESULTS: In men with a history of MI, there was a decrease of 0.1 to 0.2 quality-adjusted life years and 0.5 to 0.6 quality-adjusted life years across all ages with short-term HT and long-term HT, respectively, compared with no HT. In men without MI, receipt of short-term or long-term HT was associated with a QALE benefit versus no HT in all cohorts. Among men without MI, the optimal duration of HT was a function of age and the number of MI risk factors. Long-term HT improved QALE (range, 1.4-5.4 years) for men aged 50 or 60 years except those with MI; whereas, for men aged 70 years with 4 cardiac risk factors, short-term and long-term HT yielded identical QALE. CONCLUSIONS: Men who received RT for high-risk prostate cancer and had a history of MI experienced net harm when they received HT. Men without MI gained a QALE benefit from HT, even if they had up to 4 cardiac risk factors. The optimal duration of HT is a function of patient age and the number of cardiac risk factors.

Cost-effectiveness of stereotactic body radiation therapy versus surgical resection for stage I non-small cell lung cancer.

BACKGROUND: The traditional treatment for clearly operable (CO) patients with stage I non-small cell lung cancer (NSCLC) is lobectomy, with wedge resection (WR) and stereotactic body radiation therapy (SBRT) serving as alternatives in marginally operable (MO) patients. Given an aging population with an increasing prevalence of screening, it is likely that progressively more people will be diagnosed with stage I NSCLC, and thus it is critical to compare the cost-effectiveness of these treatments. METHODS: A Markov model was created to compare the cost-effectiveness of SBRT with WR and lobectomy for MO and CO patients, respectively. Disease, treatment, and toxicity data were extracted from the literature and varied in sensitivity analyses. A payer (Medicare) perspective was used. RESULTS: In the base case, SBRT (MO cohort), SBRT (CO cohort), WR, and lobectomy were associated with mean cost and quality-adjusted life expectancies of $42,094/8.03, $40,107/8.21, $51,487/7.93, and $49,093/8.89, respectively. In MO patients, SBRT was the dominant and thus cost-effective strategy. This result was confirmed in most deterministic sensitivity analyses as well as probabilistic sensitivity analysis, in which SBRT was most likely cost-effective up to a willingness-to-pay of more than $500,000/quality-adjusted life year. For CO patients, lobectomy was the cost-effective treatment option in the base case (incremental cost-effectiveness ratio of $13,216/quality-adjusted life year) and in nearly every sensitivity analysis. CONCLUSIONS: SBRT was nearly always the most cost-effective treatment strategy for MO patients with stage I NSCLC. In contrast, for patients with CO disease, lobectomy was the most cost-effective option.

Patient-Reported Financial Toxicity in a Population-Based Cohort of Oropharynx Cancer Survivors.

PURPOSE: Patients with oropharyngeal squamous cell carcinoma (OPSCC) are at high risk for financial toxicity (FT), but the nature, extent, and predictors of FT experienced after primary radiation therapy (RT) or surgery are poorly understood. METHODS AND MATERIALS: We used a population-based sample of patients from the Texas Cancer Registry with stage I to III OPSCC diagnosed from 2006 to 2016 and treated with primary RT or surgery. Of 1,668 eligible patients, 1,600 were sampled, 400 responded, and 396 confirmed OPSCC. Measures included the MD Anderson Symptom Inventory Head and Neck, Neck Dissection Impairment Index, and a financial toxicity instrument adapted from the Individualized Cancer Care (iCanCare) study. Multivariable logistic regression evaluated associations of exposures with outcomes. RESULTS: Of 396 analyzable respondents, 269 (68%) received primary RT and 127 (32%) surgery. The median time from diagnosis to survey was 7 years. Due to OPSCC, 54% of patients experienced material sacrifice (including 28% who reduced food spending and 6% who lost their housing), 45% worried about financial problems, and 29% experienced long-term FT. Independent factors associated with more long-term FT included female sex (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.23-2.40), Black non-Hispanic race (OR, 2.98; 95% CI, 1.26-7.09), unmarried status (OR, 1.50; 95% CI, 1.11-2.03), feeding tube use (OR, 3.98; 95% CI, 2.29-6.90), and worst versus best quartile on the MD Anderson Symptom Inventory Head and Neck (OR, 1.89; 95% CI, 1.23-2.90) and Neck Dissection Impairment Index (OR, 5.62; 95% CI, 3.79-8.34). Factors associated with less long-term FT included age >57 years (OR, 0.54; 95% CI, 0.41-0.71; P < .001) and household income ≥$80,000 (OR, 0.60; 95% CI, 0.44-0.82; P = .001). Primary RT versus surgery was not associated with long-term FT (OR, 0.92; 95% CI, 0.68-1.24). CONCLUSIONS: Oropharynx cancer survivors experience high rates of material sacrifice and long-term FT, and we identified important risk factors. Chronic symptom burden was associated with significantly worse long-term financial status, supporting the hypothesis that toxicity mitigation strategies may reduce long-term FT.

Efficacy and Quality-of-Life Following Involved Nodal Radiotherapy for Head and Neck Squamous Cell Carcinoma: The INRT-AIR Phase II Clinical Trial.

PURPOSE: Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy, but it is associated with significant dose to normal organs-at-risk (OAR). In this prospective phase II study, we investigated the efficacy and tolerability of eliminating ENI and strictly treating involved and suspicious lymph nodes (LN) with intensity-modulated radiotherapy. PATIENTS AND METHODS: Patients with newly diagnosed HNSCC of the oropharynx, larynx, and hypopharynx were eligible for enrollment. Each LN was characterized as involved or suspicious based on radiologic criteria and an in-house artificial intelligence (AI)-based classification model. Gross disease received 70 Gray (Gy) in 35 fractions and suspicious LNs were treated with 66.5 Gy, without ENI. The primary endpoint was solitary elective volume recurrence, with secondary endpoints including patterns-of-failure and patient-reported outcomes. RESULTS: Sixty-seven patients were enrolled, with 18 larynx/hypopharynx and 49 oropharynx cancer. With a median follow-up of 33.4 months, the 2-year risk of solitary elective nodal recurrence was 0%. Gastrostomy tubes were placed in 14 (21%), with median removal after 2.9 months for disease-free patients; no disease-free patient is chronically dependent. Grade I/II dermatitis was seen in 90%/10%. There was no significant decline in composite MD Anderson Dysphagia Index scores after treatment, with means of 89.1 and 92.6 at 12 and 24 months, respectively. CONCLUSIONS: These results suggest that eliminating ENI is oncologically sound for HNSCC, with highly favorable quality-of-life outcomes. Additional prospective studies are needed to support this promising paradigm before implementation in any nontrial setting.