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We performed a retrospective study to compare clinical outcomes among 51 consecutively presenting patients--38 men and 13 women, aged 46 to 74 years (median: 57)--with locally advanced human papillomavirus (HPV)-negative [...]

The recognition of the similarities between Roman epic poetry and historiography have led to valuable studies such as Joseph’s analysis of the relationship between Lucan’s Bellum Civileand Tacitus’ Histories. Traces of Lucan’s Bellum Civilecan also be observed in Tacitus’ Annals1 and 2, causing the beginning of Tiberius’ reign to look like a civil war in the making. The charismatic Germanicus sits with a supportive army on the northern frontier, much like Caesar, causing fear for Tiberius at Rome. Germanicus denies his chance to become the next Caesar and march on the city, but he exhibits other similarities with Lucan’s Caesar, including an association with Alexander the Great. Although at some points Germanicus seems to be repeating the past and reliving episodes experienced by Caesar in Bellum Civile, he prevents himself from fully realizing a Caesarian fate and becoming Lucan’s bad tyrant. The similar images, events, and themes presented by both authors create messages that reflect experiences from the authors’ own lives during dangerous times.

The landscape of care for early-stage non–small cell lung cancer continues to evolve. While some of the developments do not seem as dramatic as what has occurred in advanced disease in recent years, there is a continuous improvement in our ability to diagnose disease earlier and more accurately. We have an increased understanding of the diversity of early-stage disease and how to better tailor treatments to make them more tolerable without impacting efficacy. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncologypublish this annual update to help readers keep pace with these important developments. Experts in the care of early-stage lung cancer patients have provided focused updates across multiple areas including screening, pathology, staging, surgical techniques and novel technologies, adjuvant therapy, radiotherapy, surveillance, disparities, and quality of life. The source for information includes large academic meetings, the published literature, or novel unpublished data from other international oncology assemblies.

Lung cancer is the leading cause of cancer death worldwide. Recurrence rates at all stages are high, but evidence-based post-treatment surveillance imaging strategies to detect recurrence are poorly defined, and salvage options are frequently limited. A number of national and international oncology guidelines address post-treatment imaging, but are largely based on low-level, retrospective evidence because of a paucity of high-quality data, particularly in regard to cost-effectiveness and quality-of-life endpoints. Given the lack of randomized data addressing appropriate surveillance imaging modality and interval following definitive treatment of lung cancer, there remains an unmet clinical need. Meaningful surveillance endpoints should include the financial impact, patient quality-of-life outcomes, and access-to-care issues associated with intensive follow-up to ensure that guidelines reflect quality and sustainability. A need for prospective randomized data on the subject of imaging surveillance after definitive local therapy remains an unmet need, and an opportunity for collaboration and further research.

Variation in treatment and survival outcomes for NSCLC is high among patients with stage III or IV disease, but patients with untreated NSCLC have not been critically analyzed to evaluate for improvable outcomes. We evaluated treatment trends and their association with oncologic outcomes for NSCLC, hypothesizing that there are a substantial number of untreated patients who are similar to patients who undergo treatment.

Locally advanced non–small cell lung cancer is a heterogeneous disease with typically poor outcomes. Select patients may benefit from the integration of surgery, whereas patients with bulky, multistation, or contralateral (N3) mediastinal involvement are managed with definitive chemoradiation. Attempts to improve outcomes through induction, consolidation, or maintenance chemotherapy or radiation dose escalation have not demonstrated a survival benefit. Current research efforts focus on the integration of novel systemic agents that exploit tumor-specific driver mutations, augment antitumor immune response, or enhance radiation sensitivity.

Treatment options for medically inoperable, early-stage non-small cell lung cancer include stereotactic ablative radiotherapy (SABR) and percutaneous image guided thermal ablation. SABR is delivered over 1-5 sessions of highly conformal ablative radiation with excellent tumor control. Toxicity is depending on tumor location and anatomy but is typically mild. Studies evaluating SABR in operable NSCLC are ongoing. Thermal ablation can be delivered via radiofrequency, microwave, or cryoablation, with promising results and modest toxicity. We review the data and outcomes for these approaches and discuss ongoing studies.

There is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population.

IMPORTANCE: There is no consensus whether primary surgery followed by either adjuvant radiotherapy (RT) or adjuvant chemoradiation (CRT) or definitive CRT should be the standard treatment approach to advanced-stage hypopharyngeal squamous cell carcinoma (HP SCC). OBJECTIVES: To determine survival outcomes for patients with advanced-stage HP SCC treated at a single institution with either primary surgery plus RT or CRT or definitive CRT. EVIDENCE AND DATA ACQUISITION: We conducted a retrospective analysis of prospectively collected medical records in an institutional database for patients with HP SCC newly diagnosed between January 1999 and April 2013. Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between treatment groups using the Kaplan-Meier method, with multivariate Cox regression analysis used to control for demographic and clinicopathologic features. RESULTS: We identified 166 consecutively treated patients, 90 of whom did not meet study criteria. Of the 76 included patients, 48 (63%) had undergone definitive CRT, and 28 (37%) had undergone primary surgery with adjuvant RT or CRT. The groups were well balanced by age, smoking history, and alcohol use. Five-year OS and RFS for patients treated surgically were 66.3% and 53.6%, respectively; for patients treated with definitive CRT, OS and RFS were 41.3% and 34.5%, respectively. Multivariate Cox regression analysis showed that surgical management was associated with clinically improved OS (hazard ratio [HR], 4.78; 95% CI, 0.91-25.03; P = .06) and RFS (HR, 2.97; 95% CI, 0.76-11.53; P = .12), although the difference was not statistically significant. CONCLUSIONS AND RELEVANCE: Patients with advanced-stage HP SCC treated surgically with adjuvant RT or CRT showed a trend toward clinically improved OS and RFS compared with patients treated with definitive CRT. However, the difference was not statistically significant, and further investigation with larger controlled trials using modern approaches should be undertaken to optimize the initial management of advanced-stage HP SCC.

The objective of this study is to review a long-term single-institutional experience with helical tomotherapy (HT) for the radiotherapeutic management of head and neck cancer. From February 2006 to January 2013, a total of 301 consecutive patients with squamous cell carcinoma of the head and neck were treated with HT to a median dose of 66 Gy (range, 60 to 72 Gy). One hundred and seventy patients (56 %) underwent definitive HT and 131 patients (44 %) were treated post-operatively after surgery. There was no significant imbalance in patient or disease characteristics among patients treated with or without surgery (p> 0.05). Megavoltage computed tomography (MVCT) scans were obtained for patient alignment prior to each delivered fraction. Concurrent chemotherapy was administered to 133 patients (43 %). The 3-year estimates of overall survival, local-regional control, and disease-free survival were 76, 82, and 69 %, respectively. No difference existed with any of these endpoints among patients treated by definitive surgery versus radiation (p> 0.05). The incidence of grade 3+ acute toxicity was 30 %, with the most common related to skin erythema/desquamation, oral mucositis, esophagitis, dysguesia, and xerostomia. Post-HT esophageal stricture requiring dilatation was diagnosed in 12 %. Thirty (10 %) and 16 patients (5 %) were gastrostomy tube-dependent at 6 months and 1 year after HT, respectively. HT achieves clinical outcomes consistent with other IMRT methods and is an effective means of treatment for head neck cancer either as primary or post-operative therapy.

IMPORTANCE Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. OBJECTIVE To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. MAIN OUTCOMES AND MEASURES Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. RESULTS Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). CONCLUSIONS AND RELEVANCE Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

IMPORTANCE Radiation therapy to the head and neck has traditionally been associated with adverse effects that can affect oral health and physical functioning. Although intensity-modulated radiotherapy (IMRT) has been widely adopted as a means of decreasing toxic effects, limited clinical data exist on its potential effect on long-term quality of life. OBJECTIVE To analyze quality of life among long-term survivors of head and neck cancer treated with IMRT. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional analysis studied 50 consecutive long-term survivors of head and neck cancer from a comprehensive cancer center who had previously undergone IMRT that required bilateral neck irradiation for locally advanced disease. All patients were clinically without evidence of recurrent disease and had at least 5 years of follow-up. MAIN OUTCOMES AND MEASURES The University of Washington Quality of Life (UW-QOL) scores were reviewed for all study participants. The UW-QOL questionnaire consists of 12 domains that pertain to the degree of quality of life in the categories of pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood, and anxiety. RESULTS Five years after completion of IMRT, 42 patients (84%) reported that their health-related quality of life was “much better” or “somewhat better” than at the time of cancer diagnosis. With respect to recent health-related quality of life during the preceding 7 days at the time of completing the UW-QOL questionnaire, 40 patients (80%) treated with IMRT reported “outstanding” or “very good” levels of functioning. Five years after completion of treatment, 41 (82%) rated their overall quality of life as “outstanding” or “very good.” The lowest domain score on the UW-QOL questionnaire at 5 years pertained to salivary dysfunction. However, 42 patients (84%) reported saliva “of normal consistency” or “less saliva than normal but enough” compared with 8 (16%) reporting “too little saliva.” No patient reported having “no saliva.” CONCLUSIONS AND RELEVANCE Our findings add to the body of literature that supports the acceptance of IMRT as standard treatment for head and neck cancer. The fact that most 5-year survivors were satisfied with their quality of lives points to the ability of IMRT to preserve long-term functioning.

IMPORTANCE The diagnosis and subsequent treatment of head and neck cancer can have a potentially devastating impact on psychosocial functioning. Although the long-term physical adverse effects of radiation therapy (RT) for head and neck cancer have been well described, relatively few studies have evaluated psychosocial functioning after treatment. OBJECTIVE To determine the prevalence of self-reported depression among survivors of head and neck cancer returning for follow-up after being treated with RT. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis among 211 comprehensive cancer center patients with squamous cell carcinoma of the head and neck, who had been previously treated with RT and were disease-free with at least 1 year of follow-up. Patients with a history of mood disorder, use of mental health services in the past, or previous or current use of antidepressants or anxiolytics, excluding sleep medications, were specifically excluded. INTERVENTIONS The University of Washington Quality of Life instrument (UW-QOL), a brief, previously validated, self-administered questionnaire, was used to analyze rates of depression. MAIN OUTCOMES AND MEASURES The UW-QOL assigned scores of 0, 25, 50, 75, and 100 subjective responses of mood being “extremely depressed,” “somewhat depressed,” “neither in a good mood or depressed,” “generally good,” and “excellent,” respectively. RESULTS The mean mood score did not differ at 1, 3, and 5 years after treatment, with scores of 52.0, 55.7, and 62.1, respectively. The proportion of patients who reported their mood as “somewhat depressed” or “extremely depressed” was 17%, 15%, and 13% at 1, 3, and 5 years, respectively. Variables that were significantly associated with post-RT depression included the presence of tracheostomy tube or laryngeal stoma (P = .01), gastrostomy tube dependence (P = .01), and continued smoking at the time of follow-up (P < .001). Among the patients reporting their mood as either “somewhat depressed” or “extremely depressed” at 1, 3, and 5 years, the proportion using antidepressants at the time was 6%, 11%, and 0%, respectively. The corresponding proportion of patients actively undergoing or seeking psychotherapy and/or counseling was 3%, 6%, and 0%, respectively. CONCLUSIONS AND RELEVANCE Despite a relatively high rate of depression among patients with head and neck cancer in the post-RT setting, mental health services are severely underutilized.

SUMMARY The standard of care for unresectable, locally advanced non-small-cell lung cancer (NSCLC; stage IIIA and IIIB) in the past decade has been concomitant platinum-based chemoradiation therapy. Unfortunately, a plateau has been reached in terms of response and survival rates with the present chemotherapeutic paradigm. Targeted biological agents have significantly altered the treatment landscape for stage IV NSCLC and offer an opportunity to do the same for locally advanced NSCLC. While some early trials using unselected patients have shown modest promise for several biologic agents, the overall data remain mixed. One limitation of these trials has been the lack of patient enrichment based on molecular phenotype most likely to benefit from a particular targeted therapy. This review summarizes the most recent data for select classes of targeted agents being tested in the locally advanced NSCLC setting, and gives insights into future developments in this clinical area.

OBJECTIVE To identify potential racial disparities in the use of larynx preservation. DESIGN Retrospective database review. SETTING Academic medical center. PATIENTS The Surveillance Epidemiology and End Results (SEER) database was used to identify white, black, Hispanic, and Asian patients with stage III and IV laryngeal cancers that were diagnosed during 1991 through 2008. Patients with T4 disease or distant metastasis were intentionally excluded. MAIN OUTCOME MEASURE Univariate and multivariate logistic regression analysis, with odds ratios and 95% confidence intervals, was used to investigate the relationship between race/ethnicity and the use of larynx preservation with radiation therapy as initial therapy. RESULTS Among the 5385 cases of laryngeal cancers that met the selection criteria, the racial distribution was white (72.7%), black (16.8%), Hispanic (7.4%), and Asian (3.1%). On univariate analysis, blacks (odds ratio [OR], 0.72; 95% CI, 0.59-0.88) were significantly less likely to undergo larynx preservation. This racial disparity persisted on multivariate analysis for blacks (OR, 0.78; 95% CI, 0.63-0.96) and was still observed among patients treated more recently between 2001 and 2008 (OR, 0.74; 95% CI, 0.56-0.96). CONCLUSIONS Pronounced racial disparities exist in the use of larynx preservation therapy for locally advanced laryngeal cancer. While acknowledging the potential biases of socioeconomic factors, further research to better elucidate the underlying reasons for these findings may be warranted.

Locally advanced and recurrent colorectal cancers pose a significant therapeutic challenge. Orthovoltage intraoperative radiotherapy provides one potential means of improving disease control at the time of surgery.

Transdermal insulin transport by electroporation was measured using porcine epidermis and fluorescein-labeled insulin. Previous studies have shown that anionic lipids can enhance the electroporative transport of molecules up to 10 kDa in size. It was also shown that it is the charge and not the type of the phospholipid head group that influences transdermal transport under electroporation. Moreover, phospholipids with saturated acyl chains enhance the transport of larger molecules more as compared to those with unsaturated chains. In the current study, based on those earlier findings, the effect of 1,2-dimyristoyl-3-phosphatidylserine (DMPS) on the transdermal transport of insulin by electroporation was examined. Porcine epidermis was used as a model for skin. Transport was measured using glass vertical diffusion apparatus in which the epidermis separated the donor and receiver compartments. Negative pulses were applied across the epidermis using platinum electrodes. Results show that when electroporation was carried out in the presence of DMPS, there was greater than 20-fold enhancement of insulin transport. Furthermore, while in the presence of the phospholipid, almost all the transported insulin was detected in the receiver compartment; in the absence of added lipids, only about half the insulin transported was in the receiver compartment and an almost equal amount of insulin remained in the epidermis. Fluorescence microscopy revealed that the insulin transport was mainly through the lipid multilayer regions that surround the corneocytes.

Abedi: Abbie: Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Gilead: Speakers Bureau; Celgene: Speakers Bureau. Daly:Genentech: Research Funding. Tuscano:Takada: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Seattle Genetics: Honoraria; Amgen: Honoraria; Pharmacyclics: Research Funding; Spectrum: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Research Funding.Ibritumomab tiuxetan (Zevalin)is a CD20-directed radiotherapeutic antibody administered as part of the Zevalin therapeutic regimen indicated for the treatment of patients with relapsed or refractory, low-grade or follicular B-cell non Hodgkin'slymphoma(NHL)previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy. We hypothesized that when ibritumomab tiuxetan is added to ATG/TLI conditioning in nonmyeloablative allogeneic stem cell transplantation this would convert relapsed NHL patients in stable disease/partial response to partial response/complete response and result in durable remissions without increasing toxicity.