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BACKGROUND The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated. METHODS National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery. RESULTS Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p = 0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p = 0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p = 0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p = 0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT. CONCLUSION Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated.National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery.Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p = 0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p = 0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p = 0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p = 0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT.Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

Head and neck cancer is a diverse group of rare diseases such as neuroendocrine tumors which can be thought of as extrapulmonary small‐cell cancer. Surgery, chemotherapy, and radiation can frequently cure this disease, possibly due to early detection.

OBJECTIVE: To determine whether cervical matted lymphadenopathy (ML) is associated with outcomes in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: OPSCC patients treated at our institution with CRT were included (n = 417). ML was defined by three adjacent nodes without an intervening fat plane. Patients were stratified into favorable OPSCC (p16 + with ≤ 10 pack-years smoking history) or unfavorable OPSCC (p16- and/or > 10 pack years). Primary outcomes were overall survival (OS) and progression-free survival (PFS) and the cumulative incidences of regional recurrence (RR) and distant metastasis (DM). RESULTS: The median follow-up time for the surviving cohort was 49.9 months. In favorable OPSCC (n = 220), there were no significant associations between ML and any outcome. In unfavorable OPSCC (n = 197), ML had a significant negative impact on OS and PFS, with 3-year OS for patients without and with matted nodes at 74% and 56% (HR, 1.61, 95% CI 1.01-2.58). On multivariable Cox regression, patients with ML experienced significantly worsened OS (HR 1.65, 95% CI 1.03-2.65) and PFS (HR 1.94, 95% CI 1.28-2.93). The cumulative incidence of DM was also higher with ML (31% vs. 9%, adjusted HR 3.3, 95% CI 1.71-6.48). CONCLUSION: ML carries no prognostic importance in patients with favorable OPSCC. However, ML portends significantly worse outcomes in individuals with HPV-negative disease or a significant smoking history. Thus, ML may help risk-stratify this latter population for treatment intensification, but does not seem to be a contraindication for treatment de-escalation in the former.

The Arcsecond Space Telescope Enabling Research in Astrophysics (ASTERIA) was a 6-unit CubeSat technology demonstration mission that was built at NASA’s Jet Propulsion Laboratory (JPL) and deployed from the International Space Station (ISS) on November 20th, 2017. After successfully completing its 90-day primary mission that demonstrated arcsecond-level line-of-sight pointing and focal plane thermal stability for exoplanet detection, it entered an extended mission performing onboard software demonstrations alongside science until end of mission in December 2019. At the end of its lifetime it was being used as a demonstration platform for several experiments, including low earth orbit (LEO) optical navigation operations. With its visible light astrometric camera and stable attitude control system, the ASTERIA spacecraft showed itself to be a capable platform for the imaging of geosynchronous satellites from LEO. This paper will describe the imagery attained in flight and also the image processing algorithms that were developed to render that imagery into navigation quality data. These algorithms dealt with hot pixel filtering, noise modeling, attitude registration, star signal rejection and satellite signal identification. Brightness prediction algorithms used for target selection will also be discussed.

Background The optimal regimen of chemotherapy and reirradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multicenter phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Materials and methods Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS ≥ 70 were eligible for this trial. Cetuximab 400 mg/m2 was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2 and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated radiotherapy to a dose of 60–66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. Results From 2009 to 2013, 48 patients enrolled on this trial, 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36–85). Treatment was feasible and only 1 patient did not complete the treatment course. Common grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight grade 3 late toxicities were observed, four of which were swallowing related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (P = 0.01). OS was not associated with radiation dose, surgery before re-XRT or interval from prior XRT. Conclusions Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. ClinicalTrials.Gov Identifier NCT00833261

Importance A significant subset of patients with stage II/III non–small cell lung cancer (NSCLC) cannot receive standard concurrent chemoradiotherapy owing to the risk of toxic effects outweighing potential benefits. Without concurrent chemotherapy, however, the efficacy of conventional radiotherapy is reduced. Objective To determine whether hypofractionated image-guided radiotherapy (IGRT) would improve overall survival in patients with stage II/III NSCLC who could not receive concurrent chemoradiotherapy and therefore were traditionally relegated to receiving only conventionally fractionated radiotherapy (CFRT). Design, Setting, and Participants This nonblinded, phase 3 randomized clinical study enrolled 103 patients and analyzed 96 patients with stage II/III NSCLC and Zubrod performance status of at least 2, with greater than 10% weight loss in the previous 6 months, and/or who were ineligible for concurrent chemoradiotherapy after oncology consultation. Enrollment occurred at multiple US institutions. Patients were enrolled from November 13, 2012, to August 28, 2018, with a median follow-up of 8.7 (3.6-19.9) months. Data were analyzed from September 14, 2018, to April 11, 2021. Interventions Eligible patients were randomized to hypofractionated IGRT (60 Gy in 15 fractions) vs CFRT (60 Gy in 30 fractions). Main Outcomes and Measures The primary end point was 1-year overall survival. Results A total of 103 patients (96 of whom were analyzed [63 men (65.6%); mean (SD) age, 71.0 (10.2) years (range, 50-90 years)]) were randomized to hypofractionated IGRT (n = 50) or CFRT (n = 46) when a planned interim analysis suggested futility in reaching the primary end point, and the study was closed to further accrual. There was no statistically significant difference between the treatment groups for 1-year overall survival (37.7% [95% CI, 24.2%-51.0%] for hypofractionated IGRT vs 44.6% [95% CI, 29.9%-58.3%] for CFRT;P = .29). There were also no significant differences in median overall survival, progression-free survival, time to local failure, time to distant metastasis, and toxic effects of grade 3 or greater between the 2 treatment groups. Conclusions and Relevance This phase 3 randomized clinical trial found that hypofractionated IGRT (60 Gy in 15 fractions) was not superior to CFRT (60 Gy in 30 fractions) for patients with stage II/III NSCLC ineligible for concurrent chemoradiotherapy. Further studies are needed to verify equivalence between these radiotherapy regimens. Regardless, for well-selected patients with NSCLC (ie, peripheral primary tumors and limited mediastinal/hilar adenopathy), the convenience of hypofractionated radiotherapy regimens may offer an appropriate treatment option. Trial Registration ClinicalTrials.gov Identifier:NCT01459497

Objectives We aimed to assess the association between premorbid obesity, measured using body mass index (BMI) and lung cancer-related mortality, through a systematic review and meta-analysis. Materials and Methods Observational studies reporting statistical measures of association between premorbid BMI categories and lung cancer-related mortality were included in our study. We estimated hazard ratios (aHR) with 95% confidence intervals (CI), comparing lung cancer-related mortality across BMI categories. The main outcome measure was lung cancer-related mortality in obese (BMI≥30kg/m 2 ) and overweight participants (BMI 25.0–29.9kg/m 2 ), compared with normal BMI participants. Results We included 14 studies (including 2 pooled cohort studies) comprising 3,008,137 cancer-free participants at inception, reporting 28,592 lung cancer-related deaths. On meta-analysis, we observed a significantly lower lung cancer-related mortality in overweight (aHR, 0.76; 95% CI, 0.68–0.85) and obese (aHR, 0.68, 95% CI; 0.57–0.81) participants as compared to participants with normal BMI, with considerable heterogeneity; after excluding one study with large effect size, a more conservative and consistent association was observed between BMI and lung cancer-related mortality (overweight vs. normal BMI: aHR, 0.84; 95% CI, 0.79–0.90; obese vs. normal BMI: aHR, 0.81; 95% CI, 0.75–0.87), with moderate heterogeneity. Were similar in men vs. women, non-smokers vs. smokers, and Western vs Asia-Pacific populations. Conclusions Based on meta-analysis, we observed an independent protective association between premorbid obesity and lung cancer-related mortality. This association was observed across sex, smoking status and geographic region. Further studies are needed to prospectively study this association.

The purpose of this study is to compare the rates of recurrent VTE among cancer patients treated with parenteral agents to the oral anticoagulants. This single-center study was a retrospective chart review of cancer patients with recurrent VTE between January 1, 2009 and December 31, 2014. The primary outcome of the study is the rate of recurrent VTE in patients who received a parenteral anticoagulant (enoxaparin, dalteparin, fondaparinux) versus those who received oral anticoagulants (warfarin and rivaroxaban). Other outcomes investigated include risk factors associated with recurrent VTE events and influence of third-party payer on anticoagulant selection. Four hundred fifty-seven patients met inclusion criteria (178 in the oral anticoagulant group and 279 in the parenteral anticoagulant group). Patients with Medicare were more likely to have received an oral anticoagulant (P = 0.003) and patients with private insurance were more likely to have received a parenteral anticoagulant (P = 0.004). There were 23 recurrent VTE events, 12 events (6.7 %) in the oral anticoagulant group and 11 events (3.94 %) in the parenteral group (P = 0.182). The only significant risk factor noted to increase risk of recurrent VTE was the presence of an IVC filter (adjusted OR 4.38, 95 % CI 1.67–11.53, P = 0.003). While there is no statistical difference in VTE events between groups, the oral anticoagulant group numerically had a higher rate. Important associations were found to have an influence on anticoagulant selection and risk of recurrent VTE. These factors must be incorporated into decision making when treating cancer patients with VTE.

BACKGROUND Cutaneous adnexal adenocarcinoma is a rare cancer that is occasionally human epidermal growth factor receptor-2 (HER-2)-positive, and demonstrates variable response to HER-2 inhibitors. METHODS We report a case of adnexal adenocarcinoma of the scalp in a 56-year-old man. He underwent wide local excision with cervical node dissection followed by radiation, but had extensive local recurrence. RESULTS Pathology demonstrated a poorly differentiated adnexal adenocarcinoma with HER-2 overexpression by immunohistochemistry (IHC) and high HER-2 gene amplification by fluorescence in situ hybridization. The patient was treated with trastuzumab-based therapy with dramatic response and clinical resolution of the tumor. Upon pausing trastuzumab, he developed local relapse, but had an excellent response to restarting trastuzumab monotherapy. He lacks visible disease 43 months after the initial diagnosis. CONCLUSION We believe the exquisite sensitivity of the primary carcinoma and subsequent recurrence to trastuzumab therapy was due to strong HER-2 expression both at the protein and gene level. © 2017 Wiley Periodicals, Inc. Head Neck 39: E69-E71, 2017.

The COVID-19 pandemic demands reassessment of head and neck oncology treatment paradigms. Head and neck cancer (HNC) patients are generally at high-risk for COVID-19 infection and severe adverse outcomes. Further, there are new, multilevel COVID-19-specific risks to patients, surgeons, health care workers (HCWs), institutions and society. Urgent guidance in the delivery of safe, quality head and neck oncologic care is needed. Novel barriers to safe HNC surgery include: (1) imperfect presurgical screening for COVID-19; (2) prolonged SARS-CoV-2 aerosolization; (3) occurrence of multiple, potentially lengthy, aerosol generating procedures (AGPs) within a single surgery; (4) potential incompatibility of enhanced personal protective equipment (PPE) with routine operative equipment; (5) existential or anticipated PPE shortages. Additionally, novel, COVID-19-specific multilevel risks to HNC patients, HCWs and institutions, and society include: use of immunosuppressive therapy, nosocomial COVID-19 transmission, institutional COVID-19 outbreaks, and, at some locations, societal resource deficiencies requiring health care rationing. Traditional head and neck oncology doctrines require reassessment given the extraordinary COVID-19-specific risks of surgery. Emergent, comprehensive management of these novel, multilevel surgical risks are needed. Until these risks are managed, we temporarily favor nonsurgical therapy over surgery for most mucosal squamous cell carcinomas, wherein surgery and nonsurgical therapy are both first-line options. Where surgery is traditionally preferred, we recommend multidisciplinary evaluation of multilevel surgical-risks, discussion of possible alternative nonsurgical therapies and shared-decision-making with the patient. Where surgery remains indicated, we recommend judicious preoperative planning and development of COVID-19-specific perioperative protocols to maximize the safety and quality of surgical and oncologic care.

e21571 Background: ALK -targeting drugs and SABR are combined in patients with metastatic cancer, anecdotally yielding clinical benefit. However, the precise impact of the combination and the optimal time to introduce SABR remain unknown. Methods: This completed phase 2 study (NCT02513667) had a primary objective of doubling progression free survival (PFS) for ALK+ lung adenocarcinoma patients by consolidating all remaining disease with SABR, 8-10 weeks after ceritinib initiation. Patients who then progressed could receive repeat SABR as long as they then resumed ceritinib. Patients were divided into ALK-inhibitor naïve vs previously treated cohorts. Oligometastatic disease was NOT a requirement for study entry, CNS disease was permitted. Blood was serially analyzed for variation in 1. blood cfDNA detection of resistance mechanisms 2. flow cytometric analysis of white cell populations. Results: 14 patients were enrolled out of a planned 33; 7 female; 3 hispanic/latino; median age was 53 years (range 31-78); 5 patients had previously received crizotinib. 4 patients stopped ceritinib within 30 days due to toxicity, despite dose reductions or with-food administration. However, all patients still completed initial SABR consistent with protocol time-points. Patients predominantly had thoracic disease irradiated (11/14, 78%). Two patients had only brain metastases treated and 1 had bone only metastases treated. 4 had one fraction SBRT regimens (16-24 Gy per fraction) delivered to disease, 3 had three fraction SBRT regimens (9-11 Gy per fraction) delivered to disease, and 7 had five fraction SBRT or 15 fraction hypofractionated regimens (6 Gy per fraction or 3Gy per fraction, respectively) delivered to disease. Disease control in all irradiated areas was 100%. There was no significant grade 3 or higher toxicity associated with radiation. Broad variability in baseline and serial levels of circulating PMN-MDSC, VEGFR2, FoxP3+, CD56+CD16+ and various T-cell populations showed no clinical correlation. The trial terminated early due to increased use of alternative targeted therapies, thus the primary endpoint was not met. 8 patients had CR/PR/SD as best response. Including those who did not tolerate ceritinib, median PFS was 12 months, max of 31 months with 1 ongoing response. Conclusions: Consolidative SABR after ALK therapy is well tolerated, can be repeated and may prolong PFS compared to drug alone. Ceritinib toxicity meant higher rates of discontinuation but this did not prevent consolidative SABR in any patient. Clinical trial information: NCT02513667.

BACKGROUND This study sought to determine the oncologic impact of delays to surgery, radiotherapy, and completion of therapy in patients with head and neck squamous cell carcinoma. METHODS The impact of biopsy to surgery (BTS) time, surgery to start of radiation time (STSR), and radiation treatment time (RTT) on locoregional recurrence (LRR), distant metastases (DMs), and cancer-specific mortality (CSM) was examined. The cumulative incidences (CI) of LRR, DMs, and CSM were examined using Fine-Gray testing. RESULTS A total of 277 patients treated with surgery and adjuvant radiotherapy were analyzed. On multivariable testing, BTS >50 days was associated with DM (P = .03), whereas RTT and STSR were not. RTT >43 days was associated with LRR (P = .02) in patients with non-p16-positive-oropharynx cancer. CONCLUSIONS An increase in DM appears to be the mechanism by which prolonged time to treatment initiation leads to worse overall survival. Prolonged RTT has the greatest impact on patients with non-p16 positive oropharynx cancers.

Purpose Patients with stage IV non–small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse. Patients and Methods Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated. Results Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated. Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field. Two grade 3 toxicities were radiation related. Zero of 13 patients tested were positive for an EGFR mutation. Conclusion Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high PFS and OS, substantially greater than historical values for patients who only received systemic agents.

Nab-paclitaxel might impact efficacy of radiation for head and neck (H&N) cancer. Nab-paclitaxel, cisplatin, cetuximab, and radiation were evaluated in patients with locally advanced head and neck cancer in this phase I/II trial. Median follow-up was 24 months for 34 patients. The maximum tolerated dose of nab-paclitaxel was 20 mg/m2 with 20 mg/m2 cisplatin and 250 mg/m2 cetuximab. The 2-year progression-free survival (PFS) was 60% (95% confidence interval (CI) 0.42, 0.78), local control 71% (95% CI 0.55, 0.87), and overall survival 68% (95% CI 0.50, 0.86). This is the first study evaluating these agents with radiation in humans, with similar 2-year PFS as historic control.

Importance There is a growing debate on the relative benefits of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery, especially for patients with human papillomavirus (HPV)-driven disease. Objective To characterize the recent patterns of care in and overall survival (OS) outcomes following the use of adjuvant CRT and B-PORT after primary surgery for OPSCC. Design, Setting, and Participants Retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy between 2010 and 2012 at Commission on Cancer–accredited facilities. The data analysis was performed between June 15, 2015, and May 4, 2016. Main Outcomes and Measures The primary outcomes were prevalence of CRT and B-PORT, and OS. The primary predictors were HPV positivity and high-risk pathologic features (HRPFs) (extracapsular extension and positive surgical margins). Results Of the 1409 patients (1153 [82%] male; median age, 57 [interquartile range {IQR}, 51-63] years), 873 (62%) and 789 (56%) patients received CRT and B-PORT, respectively; most patients (n = 583 [79%]) with HRPFs received CRT, and many patients (n = 227 [40%]) without HRPFs received CRT. Multivariable predictors of CRT included adverse pathologic features (extracapsular extension [OR, 6.99; 95% CI, 5.22-9.35], positive surgical margins [OR, 2.07; 95% CI, 1.50-2.87], ≥6 involved nodes [OR, 2.34; 95% CI, 1.39-3.92], or low-neck disease [OR, 1.52; 95% CI, 1.01-2.28]), and treatment at a nonacademic institution (OR, 1.59 [95% CI, 1.21-2.10] for comprehensive community cancer center vs academic program). Patients with HPV-positive disease (OR, 0.47; 95% CI, 0.33-0.68) were less likely to receive CRT; this decrease was limited to absent HRPF treated at academic institutions (n = 173, 44 [25%] received CRT). With a median follow-up of surviving patients of 27 (IQR, 21-33) months, the 2-year OS probability was 92% (95% CI, 90%-94%). Multivariable analysis including age, sex, pathologic T stage, 6 or more positive nodes, and educational status confirmed the prognostic impact of HPV positivity (hazard ratio [HR], 0.41; 95% CI, 0.21-0.80) and HRPFs (positive surgical margins [HR, 2.15; 95% CI, 1.27-3.66] and ≥6 involved nodes [HR, 2.11; 95% CI, 1.13-3.93]), but neither CRT (HR, 1.27; 95% CI, 0.70-2.30) nor B-PORT (HR, 1.04; 95% CI, 0.63-1.73) was associated with improved OS. Conclusions and Relevance Postoperative CRT and B-PORT following resection of OPSCC were dependent on factors beyond HRPFs, including HPV status and treatment at an academic institution. No benefit was seen with intensified adjuvant therapy, supporting enrollment of the HPV-positive population into deintensification trials.

Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site; 2) previously resected disease with mediastinal relapse; or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.

Objective. To determine the effect of treatment sequence of multimodal therapy for clinically advanced squamous cell carcinoma (SCC) of the oral cavity (OC) with mandible invasion. Study Design. Case series with chart review. Setting. University-based, tertiary care hospitals. Subjects and Methods. The authors retrospectively analyzed 70 patients presenting between January 2000 and January 2010 with newly diagnosed, previously untreated SCC of the OC with mandible invasion that we deemed resectable (stages IVa, b). Patients with evidence of distant metastases or a second primary malignancy were excluded. All patients were presented at a multidisciplinary tumor board for pro- spective planning of trimodality therapy (surgery, radiation therapy, chemotherapy). When performed, surgery included segmental mandibulectomy. Radiotherapy was delivered using standard intensity-modulated radiation therapy tech- nique. Study patients were divided into 2 groups: group 1 received induction chemotherapy and/or concurrent che- moradiation followed by surgery, and group 2 was treated with primary resection followed by chemoradiation. Main Outcome Measure. Progression-free survival (PFS). Results. Eighteen patients (26%) comprised group 1, and 52 patients (74%) comprised group 2. The groups were matched in oral cavity subsite, tumor differentiation, tumor characteristics of aggressiveness (perineural and lymphovascular invasion), extent of mandible invasion, and cervical node status. The 5-year PFS for group 1 (33.3%) was not significantly different from that for group 2( 32.3%;P = .643). Conclusion. Advanced OC cancer with mandible invasion is an ominous disease. Although treatment must be individua- lized, our data suggest no clear advantage to any specific sequence of multimodality therapy affecting PFS.

Introduction Pemetrexed is an effective and a tolerable drug in advanced non-small cell lung cancer (NSCLC). This study sought to ascertain maximum tolerated dose (MTD) and phase II dose of carboplatin or cisplatin given with pemetrexed and concurrent chest radiation therapy (CRT) in locally advanced NSCLC. Methods Eligible, previously untreated patients were enrolled with the initial intent of establishing the MTD of both weekly cisplatin or carboplatin combined with pemetrexed 500 mg/m 2 every 3 weeks and concurrent CRT in an alternating, two arm, phase I trial. Secondary objectives included response rate and toxicity. The protocol was subsequently amended to establish the safety of planned phase II doses of cisplatin or carboplatin combined with pemetrexed 500 mg/m 2 given every 3 weeks × 3 cycles with CRT. Results Patients received pemetrexed combined with carboplatin area under curve=2 ( n = 9), cisplatin 30 mg/m 2 ( n = 9), or cisplatin 75 mg/m 2 ( n = 4). One dose-limiting toxicity occurred in both the carboplatin and in the cisplatin 30 mg/m 2 cohorts. No dose-limiting toxicities occurred in the cisplatin 75 mg/m 2 cohort. Because these are standard doses without radiation therapy in lung cancer, there was no further dose escalation. Partial response rates were 11% (carboplatin) and 46% (combined cisplatin). Stable disease rates were 33% (carboplatin) and 46% (combined cisplatin). Two patients receiving carboplatin experienced disease progression. Conclusions The MTD of cisplatin combined with pemetrexed was not reached. Based on these and Cancer and Leukemia Group B 30407 results, pemetrexed with either carboplatin or cisplatin at full systemic doses with CRT seems to be well tolerated. A multicenter, randomized phase II trial of both regimens is underway.

Importance Patterns-of-failure studies suggest that in metastatic non–small-cell lung cancer (NSCLC) sites of gross disease at presentation are the first to progress when treated with chemotherapy. This knowledge has led to increased adoption of local ablative radiation therapy in patients with stage IV NSCLC, though prospective randomized evidence is limited. Objective To determine if intervening with noninvasive stereotactic ablative radiotherapy (SAbR) prior to maintenance chemotherapy in patients with non–progressive limited metastatic NSCLC after induction therapy led to significant improvements in progression-free survival (PFS). Design, Setting, and Participants This is a single-institution randomized phase 2 study of maintenance chemotherapy alone vs SAbR followed by maintenance chemotherapy for patients with limited metastatic NSCLC (primary plus up to 5 metastatic sites) whose tumors did not possessEGFR-targetable orALK-targetable mutations but did achieve a partial response or stable disease after induction chemotherapy. Interventions Maintenance chemotherapy or SAbR to all sites of gross disease (including SAbR or hypofractionated radiation to the primary) followed by maintenance chemotherapy. Main Outcomes and Measures The primary end point was PFS; secondary end points included toxic effects, local and distant tumor control, patterns of failure, and overall survival. Results A total of 29 patients (9 women and 20 men) were enrolled; 14 patients (median [range] age, 63.5 [51.0-78.0] years) were allocated to the SAbR-plus-maintenance chemotherapy arm, and 15 patients (median [range] age, 70.0 [51.0-79.0] years) were allocated to the maintenance chemotherapy–alone arm. The trial was stopped to accrual early after an interim analysis found a significant improvement in PFS in the SAbR-plus-maintenance chemotherapy arm of 9.7 months vs 3.5 months in the maintenance chemotherapy–alone arm (P = .01). Toxic effects were similar in both arms. There were no in-field failures with fewer overall recurrences in the SAbR arm while those patients receiving maintenance therapy alone had progression at existing sites of disease and distantly. Conclusions and Relevance Consolidative SAbR prior to maintenance chemotherapy appeared beneficial, nearly tripling PFS in patients with limited metastatic NSCLC compared with maintenance chemotherapy alone, with no difference in toxic effects. The irradiation prevented local failures in original disease, the most likely sites of first recurrence. Furthermore, PFS for patients with limited metastatic disease appeared similar to those patients with a greater metastatic burden, further arguing for the potential benefits of local therapy in limited metastatic settings. Trial Registration clinicaltrials.gov Identifier:NCT02045446

Introduction The current standard of care for good performance status patients with locally advanced non-small cell lung carcinoma is concurrent chemoradiation, although a clearly superior regimen has not been identified. Docetaxel has been shown to possess good single-agent activity against non-small cell lung cancer (NSCLC) and radiosensitizing properties, both alone and synergistically with carboplatin. We undertook this phase II study to determine the safety and efficacy of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation for the treatment of locally advanced NSCLC. Methods Sixty-seven patients having previously untreated stage IIIA or IIIB unresectable NSCLC were enrolled, with 61 patients evaluated for endpoints. Docetaxel 20 mg/m 2 IV infusion over 30 minutes followed by carboplatin area under the curve=2 over 30 minutes was administered weekly during concurrent thoracic radiotherapy. After 3 week rest, consolidation docetaxel 75 mg/m 2 IV infusion over 60 minutes and carboplatin area under the curve=6 over 30 minutes was administered every 3 weeks for two cycles. Concurrent thoracic radiation consisted of 45 Gy (1.8 Gy fractions 5 d/wk for first 5 weeks) followed by 18 Gy boost (2.0 Gy fractions 5 d/wk for 2 weeks) for a total dose of 63 Gy. Results One and 2 years overall survival rates were 45 and 20%, respectively. Progression free survival at 1 year was 27%. Median survival time was 12 months. Median time to progression was 8 months. The primary hematologic toxicity was leukopenia. The primary nonhematologic toxicity was esophagitis. Conclusion The administered regimen of weekly docetaxel-carboplatin and concurrent radiation therapy followed by docetaxel-carboplatin consolidation has acceptable toxicity profile. However, the overall survivals at 1 and 2 years are somewhat disappointing.

The majority of non-small cell lung cancer patients present with locally advanced disease that may not be resectable. A single modality treatment such as thoracic radiotherapy often results in an inferior outcome when compared to combined modality treatment. Various combinations of radiotherapy, chemotherapy, and surgery have been tested in patients with locally advanced non-small-celllung cancer with promising results. The favorable results of the combined modality treatment are accompanied by a corresponding increase in treatment related morbidity. In this article, the results of the application of combined modality treatments in the management of locally advanced non-small cell lung cancer are reviewed.

Summary Objectives Despite several randomized trials, the optimal chemotherapy paradigm for locally advanced oropharyngeal carcinoma (OPSCC) is controversial. This population-based analysis assessed the overall survival (OS) benefit of induction chemotherapy (IC) for patients with stage III–IVB OPSCC. Materials and Methods Patients in the National Cancer Database with stage III–IVA-B OPSCC treated with curative-dose radiotherapy and IC or concurrent chemotherapy (CRT) between 2003 and 2011 were eligible. The primary outcome was OS, and secondary endpoints included OS for high-risk (T4 and/or N3 disease) and human papillomavirus (HPV) subsets. Results Of the 14,856 analyzed patients, 78% and 22% received CRT and IC, respectively. With a median follow-up for surviving patients of 44 months, the 5-year OS probability for the entire cohort was 66% (66% CRT vs. 64% IC, p = 0.022). Multivariable survival analysis showed no significant difference between CRT and IC (hazard ratio, HR, 0.95 for IC, p = 0.255), and sensitivity analyses to adjust for immortal time bias brought the HR to 1.0 (p = 0.859). There was also no OS difference for high-risk patients. There was a trend in favor of CRT for HPV-positive OPSCC (HR 1.63 with IC, p = 0.064), with a significant OS benefit for HPV-negative, high-risk OPSCC (HR 0.63, p = 0.048). Conclusion For the vast majority of patients, including HPV-positive individuals, there was no difference in OS with IC, arguing for CRT to remain as the standard therapy. Subset analysis revealed a small cohort of aggressive cancer (T4/N3 HPV-negative) which may benefit from from IC, although selection bias could not be ruled out.

TPS6098 Background: ATC is a rare thyroid cancer with a highly aggressive clinical course. Median OS is 3-4 months and 90% of patients die within 1 year of the diagnosis. There are no effective treatment options in metastatic disease. Targeted therapies to ALK and BRAF are occasionally associated with dramatic responses. Retinoblastoma (Rb) inhibits cell cycle progression and is inactivated by CDK 4/6, which is the target for ribociclib. Nearly all differentiated thyroid cancers are Rb negative, conversely nearly 100% of ATC expresses intact Rb which may be crucial for rapid cell cycle progression. Ribociclib is a CDK 4/6 inhibitors that slows cell cycle progression and DNA replication in tumors with functional Rb. The p16 protein similarly inhibits CDK4/6; if p16 levels are high Rb is phosphorylated and thus inactive. p16 is low in ATC, and from our comprehensive genomic analysis 30% of ATC lacks the p16 gene CDKN2a. Most ATC demonstrates PI3K/Akt/mTOR abnormalities, this pathway represents an attractive target in ATC. The mTOR inhibitor everolimus has shown promising efficacy in ATC cell lines, especially in those with TSC2 mutation whose wild type negatively regulates mTOR. Methods: The combination of everolimus and ribociclib targets mutations/abnormalities that are frequently seen in ATC, and is tolerable based on Phase I/II trial results in the latest arm of the biomarker/oncogene driven ATC Master Protocol . This open-label trial treats metastatic Rb+ ATC patients with p16-/ CDKN2a-. Treatment is ribociclib 400 mg + everolimus 5 mg QD. The primary endpoint is the overall response rate; secondary endpoints are PFS, OS, safety and toxicity. Exploratory objectives include if tissue biomarkers or mutations noted on Next Generation Sequencing correlate for enhanced/impaired response to combination therapy. Simon's two-stage design will be used with the null hypothesis that the true response rate is 5%, this will be tested against a one-sided alternative. In the first stage, 9 patients will be accrued. If no response in these 9 patients, the study will be stopped. Otherwise, 21 additional patients will be accrued for a total of 30. Clinical trial information: NCT02289144.

There have been few reports of acute liver failure (ALF), with encephalopathy and coagulopathy, caused by infiltration of the liver by malignant cells. We describe a case series of 27 patients with ALF caused by malignancy. We examined a large, multicenter ALF registry (1910 patients; mean age, 47.1 ± 13.9 y) and found only 27 cases (1.4%) of ALF attributed to malignancy. Twenty cases (74%) presented with abdominal pain and 11 presented with ascites. The most common malignancies included lymphoma or leukemia (33%), breast cancer, (30%), and colon cancer (7%); 90% of the patients with lymphoma or leukemia had no history of cancer, compared with 25% of patients with breast cancer. Overall, 44% of the patients had evidence of liver masses on imaging. Diagnosis was confirmed by biopsy in 15 cases (55%) and by autopsy for 6 cases. Twenty-four patients (89%) died within 3 weeks of ALF.

Objectives:Compare functional and survival outcomes between patients with advanced stage head and neck squamous cell cancer (HNSCC) treated with primary transoral surgery versus primary chemotherapy and radiation.Methods:Retrospective case-control trial at an academic tertiary referral center. We identified a surgical group (SG) comprised of 37 patients with previously untreated stage III and IV HNSCC who underwent either transoral robotic surgery (TORS) or transoral laser microsurgery (TLMS) and a nonsurgical group (NSG) of 75 patients treated with primary chemotherapy and radiation between July 2007 and November 2011. NSG was matched to SG by age, sex, tumor location, stage, tobacco and alcohol use, and ECOG status. Tracheostomy and percutaneous gastrostomy tube (PEG) rates during treatment and at follow-up, as well as survival outcomes, were examined.Results:There were no statistically significant differences in the matched variables. Significantly fewer patients in the SG compared with the NSG still h...

Background and Objectives The colon is a rare location for gastrointestinal non-Hodgkin's lymphoma (NHL). This study was undertaken to identify risk factors, presentation, treatment, and prognosis for primary colonic lymphoma (PCL) through review of a large tertiary care hospital system experience. Methods A retrospective review of all patients with colonic malignancy and NHL was performed using pathology and cancer registry databases from January 1989 to December 1998. Criteria for inclusion were no evidence of extraperitoneal disease, no leukemic or lymphomatous abnormalities in the blood, and disease confined to the colon. Results Seven patients met the inclusion criteria (4 male, 3 female; 33–72 years). They represented 1.4% of all NHL, 14% of gastrointestinal NHL and 0.9% of all colonic malignancies diagnosed during this period. Three of the patients had positive serology for human immunodeficiency virus; one was taking steroids chronically for Addison disease. The most common presentation was nonspecific abdominal pain. The lack of specific symptoms delayed diagnosis from 1–12 months. All patients underwent laparotomy with resection. The most common tumor location was the cecum (5/7, 71%). Regional lymph nodes were affected in all but 1 patient. All tumors were B-cell lymphomas (5 small noncleaved cell, 2 large cell). Six of 7 patients received adjuvant chemotherapy. Of the 6 patients available for follow-up four remain alive (12, 19, 23, and 25 months after diagnosis). In both patients who died the disease recurred diffusely. Conclusions The colon is a rare location for NHL. Immunosupression is the most common risk factor. Patients' frequently present with non-specific abdominal pain, this leads to lengthy delays in diagnosis. Most of these tumors are located in the cecal area. Surgery is the most widely utilized form of therapy. Although adjuvant therapy is frequently utilized, its' impact on survival is unclear. J. Surg. Oncol. 2000;74:257–262. © 2000 Wiley-Liss, Inc.

We studied the effect of cytoreductive chemotherapy in head and neck cancer and analyzed it in terms of efficacy, remission rates, and duration, as well effect on survival. Single-agent chemotherapy, which formerly was used as a palliative therapy in recurrent and metastatic disease, had little affect on survival. More recently, multi-agent chemotherapy trials have shown significantly higher response rates, but this success has not translated into an added survival benefit. These findings led to the introduction of multi-agent chemotherapy into the induction (neoadjuvant) clinical setting. In these clinical circumstances, better objective response rates were found, particularly in the previously untreated patient. Although this therapy has resulted in better control of local disease, the impact on survival is not yet clear. Adjuvant chemotherapy is most useful in patients who have a high risk of relapse. Therapy appears to decrease its incidence, particularly at distant sites. Finally, chemoradiation trials have shown that this treatment provides a survival advantage, but at the cost of a significant increase in toxicity.

TPS6085 Background: ATC is a rare tumor of thyroid epithelium affecting several hundred patients annually, but causing death in almost 100% of them. It has a dismal prognosis with currently ineffec...

6071 Background: Patients with HPV-positive head and neck squamous cell carcinoma (HPV+HNSCC) demonstrate favorable outcomes compared to HPV-negative SCC. Despite loco-regional control distant meta...

Round pneumonia is well known in the pediatric population; however, it is relatively uncommon in adults. The appearance of round pneumonia may be difficult to distinguish from lung carcinoma on anatomic images. This case illustrates a round pneumonia mimicking a pulmonary malignancy on PET/CT. In patients found to have rapid development of a round pulmonary lesion and clinical manifestations of pneumonia, it may be prudent to treat with empiric antibiotics before invasive diagnostic procedures for malignancy.

8074 Background: Stage IV NSCLC patients who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in existing sites of gross disease after systemic therapy. Cytoreduction with SBRT may aid systemic agents in prolonging survival. We decided to test this hypothesis in a multi-institutional phase II study with SBRT and erlotinib. Methods: Stage IV NSCLC patients with ≤ 6 sites of extracranial disease who failed first-line systemic therapy were eligible to receive SBRT to all sites of clinically apparent disease, utilizing equipotent fractionation schemes based on location of disease and risk of toxicity to critical normal structures, and erlotinib given daily (150 mg OD) until disease progression. Frequent SBRT fractionation schemes used included 33 Gy in 11 Gy fractions and 40 Gy in 8 Gy fractions. Safety and clinical endpoints were evaluated. Results: 23 patients (12 M: 11 F) with a median age of 67 (56-86) were enrolled in this trial with median follow-up of 14.7 months. All patients progressed through platinum-based chemotherapy, 14 with paclitaxel and 7 with pemetrexed as part of the doublet regimen. 20/23 patients received SBRT to 3 or fewer sites. Lung parenchyma and mediastinal lymph nodes represented most common sites of irradiation. Median PFS was 10.7 months and median OS was 20.8 months.A majority of patients progressed in new sites with only 4 patients failing locally. Most distant failures manifested in the liver. Only one grade 3 toxicity, pneumonitis, was radiation-related. The trial commenced before molecular profiling became standard; 5/10 patient tumors tested, however, had EGFR alterations by IHC/FISH, 0/10 were positive for an EGFR mutation. Conclusions: Use of SBRT with erlotinib for unselected stage IV NSCLC patients as a second-line therapy was well tolerated and resulted in significant PFS and OS, substantially greater than historical values for patients who only received second-line systemic agents. Debulking gross disease with local therapy results in a median PFS of nearly a year with patients relapsing most commonly in new rather than existing sites. Clinical trial information: NCT00547105.

7545 Background: Pemetrexed is a multi-targeted antifolate that inhibits the synthesis of both pyrimidines and purines. Pemetrexed is an effective new chemotherapeutic agent in advanced non-small cell lung cancer. Pemetrexed has also shown preclinical activity as a radiosensitizer in lung cancer. A phase I study was performed to establish the maximum tolerated dose (MTD) and phase 2 dose of carboplatin or cisplatin given with pemetrexed and CRT in LANSCLC. Methods: Patients (pts) with LANSCLC were enrolled. Initial intent was to establish the MTD of both weekly cisplatin and weekly carboplatin in combination with pemetrexed and CRT as an alternating two-arm phase I trial. Subsequently and based on early results from the CALGB 30407 trial (also evaluating the MTD of carboplatin), the protocol was amended to establish the safety of the planned phase II doses of cisplatin and carboplatin combined with pemetrexed 500 mg/m2 and given every 3 weeks with concurrent CRT. Dose limiting toxicity (DLT) was defined as ≥ Grade 3 hematologic or nonhematologic toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD was determined by occurrence of 2 DLTs among 6 pts in each cohort. Results: 22 pts were enrolled on 3 cohorts. All pts received pemetrexed, 9 with carboplatin AUC=2, 9 with cisplatin 30 mg/m2, and 4 with cisplatin 75 mg/m2. One DLT occurred in each of the carboplatin and cisplatin 30 mg/m2 cohorts, prompting enrollment of 3 additional patients. No DLTs were seen in the cisplatin 75 mg/m2 cohort. Conclusions: The MTD of cisplatin in combination with pemetrexed and CRT was not reached. Based on these results and those from CALGB 30407, either carboplatin AUC=5 or cisplatin 75 mg/m2 in combination with pemetrexed 500 mg/m2 given every 3 weeks with CRT appears to be well tolerated, and are currently being studied in a randomized phase II trial in pts with LANSCLC. [Table: see text]

7565 The current standard of care for good performance status patients with locally advanced non-small cell lung carcinoma is concurrent chemoradiation, although a clearly superior regimen has not ...

7560 We performed a phase I trial of orally-administered platinum (IV) complex, satraplatin to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) with concurrent definiti...

®49-year-old Hispanic male with stage IV non-squamous, non–small-cell lung cancer (NSCLC) on maintenance bevacizumab treatment, presented with progressive paresthesias over the back, abdomen, and chest; left foot numbness; unsteady gait; and mid-back pain. He had been diagnosed with advanced lung cancer 14 months prior, including bulky thoracic adenopathy, brain metastases, and malignant pleural and pericardial effusions. Imaging demonstrated no spinal, dural, or vertebral lesions. He was initially treated with pericardiectomy and whole brain radiation therapy (RT), followed by administration of six cycles carboplatin-paclitaxel plus bevacizumab then 12 cycles of bevacizumab maintenance monotherapy. To evaluate the patient’s neurologic symptoms, magnetic resonance imaging (MRI) of the spine was performed, which suggested the presence of intramedullary spinal cord metastases (ISCM) at the T4 level, with associated hemorrhage (Fig. 1A, B). Additional imaging revealed stable disease elsewhere. He was started on systemic steroids, and bevacizumab was discontinued. Neurosurgery was consulted with recommendation against surgical intervention. RT (45 Gray/25 fractions) was delivered to the intramedullary metastases. Back pain resolved, neurologic symptoms improved, and steroids were discontinued. MRI evaluation after RT demonstrated reduction in size of the metastases with resolution of hemorrhage. (Fig. 1C, D).