Diagnostic Delay in HPV-Related Oropharyngeal Squamous Cell Carcinoma.

Introduction Human papillomavirus-related (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002-2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p = 0.03). Conclusions Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment.

Diagnostic Delay in HPV-Related Oropharyngeal Squamous Cell Carcinoma

Abstract Introduction Human papillomavirus-related (HPV +) oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence and presents diagnostic challenges given its unique clinical presentation. Objective The purpose of the present study is to characterize the impact of the unique clinical presentation of HPV-related OPSCC on delays in diagnosis. Methods Retrospective review of presenting symptoms and clinical characteristics of 284 patients with OPSCC treated from 2002-2014. Delay in diagnosis was defined as the presence of any of the following: multiple non-diagnostic fine needle aspirate (FNA) biopsies; two or more courses of antibiotic therapy; surgery with incorrect preoperative diagnosis; evaluation by an otolaryngologist without further workup; or surgery without definitive postoperative diagnosis. Results p16+ tumors demonstrated a distinct clinical presentation that more commonly involved a neck mass (85.1% versus 57.3% of p16-; p < 0.001) and less frequently included odynophagia (24.6% versus 51.7% of p16-; p < 0.001). Patients who experienced diagnostic delay were more likely to have p16+ tumors (77.7% delayed versus 62.8% not delayed; p = 0.006). p16+ primary tumors were more likely to be undetectable by physical examination of the head and neck including flexible laryngoscopy (19.0% versus 6.7% of p16-; p = 0.007) and more frequently associated with nondiagnostic FNA biopsies of a cervical nodal mass (11.8% versus 3.4% of p16-, p = 0.03). Conclusions Compared with non-HPV related OPSCC, the unique clinical presentation and characteristics of HPV+ OPSCC are associated with an increased incidence of diagnostic delay. Targeted education of appropriate care providers may improve time to diagnosis and treatment.

Stereotactic body radiation therapy (SBRT) in recurrent, persistent or oligometastatic gynecological cancers.

OBJECTIVE: SBRT is a well-tolerated technique and provides local-regional control in a variety of metastatic and recurrent tumor types. The role of SBRT in extracranial recurrent, persistent, or oligometastatic gynecological tumors is not well-studied. We therefore retrospectively analyzed a sizeable number of patients in this setting. METHODS: We performed a retrospective review of 86 patients with 209 tumors treated at our institution with SBRT for recurrent, persistent, or oligometastatic extracranial gynecological tumors. The median follow-up was 20 months (range 1-91). The median SBRT dose was 24 Gy (range 10-50) delivered in a median of 4 fractions (range 1-6). The Kaplan-Meier curves and log rank tests were used to assess local control (LC) and overall survival (OS). Cox proportional hazards model was used to evaluate for covariates associated with LC and OS. RESULTS: The 1- and 3-year LC were 80% and 68% respectively. The 1- and 3-year OS were 70% and 39%. 32% of the lesions demonstrated complete response, 23% partial response and 20% stable disease. SBRT achieved better local control in smaller tumors. Toxicity was typically mild with grade 1 gastrointestinal toxicity and fatigue being the most common. Only 4.3% of treatments resulted in grade 2 or greater toxicity. There was only one case of grade 3 and no grade 4 or 5 toxicities. CONCLUSIONS: SBRT offers a high rate of local control with low incidence of toxicity, mainly grade 1 GI toxicity and fatigue, and provides effective salvage therapy for oligometastatic extracranial pelvic and extra-pelvic gynecological tumors.

Bleeding after interstitial brachytherapy for cervical cancer requiring embolization.

Cervical cancer is the third most common cancer among women worldwide and is usually managed with chemoradiation in advanced disease. This case presents a 41-year-old female with locally advanced cervical cancer who underwent combination intracavitary/interstitial brachytherapy after chemoradiation for local disease control. At her fifth brachytherapy session, one of the interstitial needles was malpositioned and lead to vascular injury with significant blood loss. She subsequently underwent emergent embolization of a branch of the right obturator artery with immediate clinical improvement and no complications. This is the first reported case of vascular injury from an interstitial brachytherapy needle that required arterial embolization for hemostasis.

How dose sparing of cardiac structures correlates with in-field heart volume and sternal displacement.

Cardiac irradiation increases the risk of coronary artery disease in patients with left-sided breast cancer. Techniques exist to reduce cardiac irradiation, but the optimum technique depends on individual patient anatomy and physiology. We investigated the correlation of delta heart volume in field (dHVIF) and sternal excursion with dose sparing in heart and left anterior descending artery (LAD) to develop quantitative predictive models for expected dose to heart and LAD. A treatment planning study was performed on 97 left-breast cancer patients who underwent whole breast radiotherapy (prescription dose = 50 Gy) under deep inspiratory breath hold (DIBH). Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy-based DIBH amplitude. The mean heart and LAD dose were compared between FB and DIBH plans and dose to the heart and LAD as a function of dHVIF and sternal excursion were determined. The [Average (STD); Range] mean heart doses from free breathing and DIBH are [120.5(65.2); 28.9 ~ 393.8] cGy and [67.5(25.1); 19.7 ~ 145.6] cGy, respectively. The mean LAD doses from free breathing and DIBH are [571.0(582.2); 42.2 ~ 2332.2] cGy and [185.9(127.0); 41.2 ~ 898.4] cGy, respectively. The mean dose reductions with DIBH are [53.1(50.6); -15.4 ~ 295.1] cGy for the heart and [385.1(513.4); -0.6 ~ 2105.8] cGy for LAD. Percent mean dose reductions to the heart and LAD with DIBH are 44% (p < 0.0001) and 67% (p < 0.0001), respectively, compared to FB. The dHVIF mean dose reduction correlation is 8.1 cGy/cc for the heart and 81.6 cGy/cc for LAD (with linear trend and y intercept: 26.0 cGy for the heart, 109.1 cGy for LAD). DIBH amplitude using sternal position was [1.3(.48); .38 ~ 2.5] cm. The DIBH amplitude mean dose reduction correlation is 14 cGy/cm for the heart and 212cGy/cm for LAD (with linear trend with y intercept: 35.6 cGy for the heart, 102.4 cGy for LAD). The strong correlation of dose sparing to the heart and LAD with dHVIF and sternal excursion suggests that mean dose sparing to heart and LAD can be predicted with either dHVIF or sternal excursion equally well. The metrics proposed could be utilized to allow providers to determine the relative dosimetric benefits of different heart-sparing techniques as early as time of consultation.

Percutaneous endoscopic gastrostomy tube dependence following chemoradiation in head and neck cancer patients.

OBJECTIVES/HYPOTHESIS: Compare long-term percutaneous endoscopic gastrostomy (PEG) tube dependence, stricture rate, and weight loss in patients receiving a prophylactic gastrostomy tube with those who initially rely on oral intake during chemoradiation for head and neck cancer. Also, to determine what other patient and treatment characteristics influence development of long-term severe dysphagia. STUDY DESIGN: Retrospective review. METHODS: Seventy-nine patients received a PEG tube and 25 did not. The prophylactic and initial oral intake groups were then analyzed to assess the primary outcomes of PEG dependence at last follow-up >1 year. RESULTS: On univariate and multivariate analysis, Zubrod score >1, prophylactic PEG placement, and higher T classification were predicted for PEG tube dependence at last follow-up at least 1 year after treatment. CONCLUSIONS: Prophylactic PEG tube, high Zubrod score, and high T stage were independent predictors for PEG tube dependence at least 1 year after treatment in patients with head and neck cancer receiving definitive chemoradiation. LEVEL OF EVIDENCE: 4.

Dosimetric feasibility of stereotactic body radiation therapy as an alternative to brachytherapy for definitive treatment of medically inoperable early stage endometrial cancer.

PURPOSE: This study was designed to evaluate the dosimetric feasibility of definitive stereotactic body radiation therapy (SBRT) for the treatment of medically inoperable early stage endometrial cancer. METHODS: CT simulation scans from 10 medically inoperable early stage endometrial cancer patients previously treated with high dose-rate (HDR) intracavitary brachytherapy were used to generate Helical Tomotherapy (HT) plans using the IMRT mode with clinical target volumes (CTVs) that included the uterus plus cervix. A prescription dose of 34 Gy in 4 fractions was used. The SBRT dosimetry was compared to the 10 prior intracavitary brachytherapy plans normalized to a standard dose. Organs at risk (OARs) evaluated were the bladder, rectum, sigmoid, femoral heads, and other bowel, including both large and small bowel. The simulation CT and daily image guidance for 4 patients treated with this technique were evaluated to assess for interfraction variation in the uterine position and effects on dosimetry. RESULTS: Compared to intracavitary brachytherapy, HT SBRT produced significantly greater overall target coverage to the uterus, boost CTV, and PTV, with exception of the V150% of the uterus. HT SBRT significantly increased dose to the rectum, bowel, and femoral heads compared to intracavitary brachytherapy, though not outside of dose tolerance limits. Review of daily image guidance for patients treated with this technique demonstrated good reproducibility with a mean overlap index of 0.87 (range, 0.74 - 0.99). CONCLUSIONS: Definitive SBRT for medically inoperable early stage endometrial cancer appears to be a feasible treatment option. Future studies are warranted to evaluate long-term clinical outcomes with this technique, compared to HDR intracavitary brachytherapy.

Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas.

IMPORTANCE: The prognostic significance of p16 in squamous cell carcinoma (SCC) of the hypopharynx (HP) and nasopharynx (NP) and relationship between human papillomavirus (HPV) and p16 is unclear. OBJECTIVES: To evaluate the prognostic significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and assess the relationship between HPV and p16 in the HP and NP. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of 172 patients with SCC of the pharynx treated with definitive radiation therapy from 2002 to 2013 at a university tertiary referral center, with tissue available for immunohistochemical analysis. The median follow-up was 30.1 months. INTERVENTIONS: A total of 118 patients were treated with chemoradiation, and 54 patients were treated with radiation alone. Immunohistochemical analysis for p16 was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using in situ hybridization, and NP tumors were tested for Epstein-Barr virus. MAIN OUTCOMES AND MEASURES: Overall survival, locoregional control, and disease-free survival were analyzed according to p16, HPV, and Epstein-Barr virus status. RESULTS: Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16 Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14% in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and NP tumors. p16 Status was a significant predictor of all clinical outcomes for patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes. CONCLUSIONS AND RELEVANCE: p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ hybridization when p16 positive.

Treatment-related complications of radiation therapy after radical prostatectomy: comparative effectiveness of intensity-modulated versus conformal radiation therapy.

Intensity-modulated radiation therapy (IMRT) is frequently utilized after prostatectomy without strong evidence for an improvement in outcomes compared to conformal radiation therapy (RT). We analyzed a large group of patients treated with RT after radical prostatectomy (RP) to compare complications after IMRT and CRT. The Surveillance, Epidemiology and End Results (SEER)-Medicare database was queried to identify male Medicare beneficiaries aged 66 years or older who underwent prostatectomy with 1+ adverse pathologic features and received postprostatectomy RT between 1995 and 2007. Chi-square test was used to compare baseline characteristics between the treatment groups. First complication events, based upon administrative procedure or diagnosis codes occurring >1 year after start of RT, were compared for IMRT versus CRT groups. Propensity score adjustment was performed to adjust for potential confounders. Multivariable Cox proportional hazards models of time to first complication were performed. A total of 1686 patients were identified who received RT after RP (IMRT = 634, CRT = 1052). Patients treated with IMRT were more likely to be diagnosed after 2004 (P < 0.001), have minimally invasive prostatectomy (P < 0.001) and have positive margins (P = 0.019). IMRT use increased over time. After propensity score adjustment, IMRT was associated with lower rate of gastrointestinal (GI) complications, and higher rate of genitourinary-incontinence complications, compared to CRT. The observed outcomes after IMRT must be considered when determining the optimal approach for postprostatectomy RT and warrant additional study.

Pilot Study of iPad Incorporation Into Graduate Medical Education.

BACKGROUND: Increased documentation and charting requirements are challenging for residents, given duty hour limits. Use of mobile electronic devices may help residents complete these tasks efficiently. OBJECTIVE: To collect initial data on usage rates, information technology (IT) support requirements, and resident use of iPads during training. METHODS: In this pilot study, we provided 12 residents/fellows from various specialties at the University of Virginia with an iPad with IT support. The system used a virtual private network with access to the institution's electronic health record. Participants were allowed to develop their own methods and systems for personalized iPad use, and after 9 months they provided data on the utility of the iPad. Feedback from the IT team also was obtained. RESULTS: Average iPad use was 2.1 h/d (range, 0.5-6 h/d). The average self-reported reduction in administrative work due to the iPad was 2.7 h/wk (range, 0-9 h/wk). A total of 75% (9 of 12) of the users would recommend universal adoption among residents and fellows. More than 90% (11 of 12) of users reported the iPad would improve communication for coordination of care. A total of 68% (8 of 12) of users reported that an iPad facilitated their activities as educators of medical students and junior residents. Residents cited slow data entry into the electronic health record and hospital areas lacking Wi-Fi connectivity as potential drawbacks to iPad use. The IT team reported minimal support time for device setup, maintenance, and upgrades, and limited security risks. CONCLUSIONS: The iPad may contribute to increased clinical efficiency, reduced hours spent on administrative tasks, and enhanced educational opportunities for residents, with minimal IT support.