Evaluating hematology/oncology clinical pharmacist activities via self-reported work sampling.

PURPOSE: Hematology/oncology clinical pharmacists' work activities have been described in previous literature, but time spent on pharmacist tasks has not been well characterized. Random work sampling (WS) is a form of activity assessment to determine the proportion of time spent in various types of work. Based on results from previous WS evaluations at University of Utah and its Huntsman Cancer Hospital, activities were changed to maximize time dedicated to clinical activities and pharmacists' benefit to providers and patients in both inpatient and ambulatory care settings. Therefore, updated random WS evaluations were completed during spring 2019 and fall 2020. METHODS: Personal digital assistant (PDA) devices were used to record hematology/oncology clinical pharmacists' onsite or remote location and work activity data. Data were collected 8 times per hour on weekdays, with a goal of 275 observations per pharmacist. Results were then classified as clinical, professional, or technical activities. RESULTS: In 2019, 9,079 observations were recorded by 31 onsite pharmacists. In 2020, 28 pharmacists recorded 8,803 observations (5,524 during onsite work and 3,279 during remote work). The overall distribution of pharmacists' work activities remained stable between 2019 and 2020, with 89% of activities classified as clinical or professional. Pharmacists spent a smaller proportion of time on in-person communication in 2020, balanced by increases in chart review and text-based communication. Onsite pharmacists reported a larger proportion of clinical activities, while remote pharmacists reported a larger proportion of professional activities. CONCLUSION: Continued WS assessment of work activity patterns will allow identification of opportunities to streamline workflows, maximize pharmacist engagement in clinical activities, and development of remote work policy.

Internet use and anxiety in people with melanoma and nonmelanoma skin cancer.

BACKGROUND: People with cancer are increasingly turning to the Internet for health-related information. OBJECTIVE: To compare the patterns of Internet use of people with skin cancer with previous findings by including people with nonmelanoma skin cancer (NMSC) using a comprehensive survey. To evaluate perceived anxiety levels and overall satisfaction after searching the Internet of people with skin cancer. METHODS & MATERIALS: We conducted a survey study and prospectively collected data from people newly diagnosed with melanoma or NMSC. RESULTS: Four hundred fifteen participants with melanoma and 400 with NMSC completed the questionnaire. Internet use and overall satisfaction with the Internet search increased more than 50% in participants with melanoma from 2005. One-third of participants with melanoma, but many fewer participants with NMSC, reported higher anxiety after Internet use. Participants who were younger, female, more highly educated, and diagnosed with melanoma were most likely to use the Internet to search for information about their diagnosis. CONCLUSION: Internet use is prevalent and increasing sharply in individuals with skin cancer. The majority of individuals describe their use of the Internet as a positive experience. Greater anxiety from searching the Internet is more common in individuals with melanoma than in those with NMSC.

Resection for esophageal cancer in the elderly.

Although studies differ in their definition of the older patient, increasing age, when considered as a continuum, is associated with greater operative mortality. Complication rates also seem to be significantly higher with advancing age, possibly because of limited physiologic reserve. As the understanding of risk factors for perioperative morbidity and mortality following esophagectomy has improved, investigators have sought to develop models for risk stratification in which patient age is a significant but not the sole determinant of prospective assessment of risk for complication or mortality. Such prognostic indicators, if validated among independent patient cohorts, can serve as useful adjuncts in decision making with appropriate clinical judgment. In addition, reported patient survival differs dramatically between rates reported by single centers and rates observed in population-based studies, with operative mortality rates typically lower in single-center reports. Although such reports usually are issued from groups with higher operative volume that might be a surrogate for surgical experience, it also is possible that the association between operation volume and improved outcomes reflects optimization of institution-specific infrastructure and/or clinical care pathways. As these processes of care evolve, they should be tailored with attention to differences in the care of older patients who have esophageal cancer. Whether widespread application of such processes of care then can lead to less perioperative mortality and fewer complications and to improved long-term survival remains untested.

Standard-unit measurement of cellular viability using dynamic light scattering optical coherence microscopy.

Dynamic light scattering optical coherence microscopy (DLS-OCM) integrates DLS, which measures diffusion or flow of particles by analyzing fluctuations in light scattered by the particles, and OCM, which achieves single-cell resolution by combining coherence and confocal gating, integratively enabling cellular-resolution 3D mapping of the diffusion coefficient, and flow velocity. The diffusion coefficient mapping has a potential for the non-destructive measurement of cellular viability in the standard unit but has not been validated yet. Here, we present DLS-OCM imaging of intra-cellular motility (ICM) as a surrogate of cellular viability. For this purpose, we have simultaneously obtained and compared ICM-contrast DLS-OCM images and calcium fluorescence-contrast images of retinal ganglion cells, and then characterized the responses of the measured ICM to a change in cellular viability induced by environmental conditions such as temperature and pH. The diffusion-coefficient-represented ICM exhibits consistent changes with the manipulated cellular viability.

Response to therapy and outcomes in oropharyngeal cancer are associated with biomarkers including human papillomavirus, epidermal growth factor receptor, gender, and smoking.

Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.

Prospective study of inner ear radiation dose and hearing loss in head-and-neck cancer patients.

PURPOSE: To determine the relationship between the radiation dose to the inner ear and long-term hearing loss. METHODS AND MATERIALS: Eligible patients included those receiving curative radiotherapy (RT) for head-and-neck cancer. After enrollment, patients underwent three-dimensional conformal RT planning and delivery (180-200 cGy/fraction) appropriate for their disease site and stage. The inner ear was contoured on axial CT planning images. Dose-volume histograms, as well as the mean and maximal dose for each structure, were calculated. Patients underwent pure tone audiometry at baseline (before treatment) and 1, 6, 12, 24, and 36 months after RT. The threshold level (the greater the value, the more hearing loss) in decibels was recorded for 250, 500, 1000, 2000, 4000, and 8000 Hz. For patients receiving predominantly unilateral RT, the contralateral ear served as the de facto control. The differences in threshold level between the ipsilateral and contralateral ears were calculated, and the temporal pattern and dose-response relation of hearing loss were analyzed using statistical methods that take into account the correlation between two ears in the same subject and repeated, sequential measurements of each subject. RESULTS: Of the 40 patients enrolled in this study, 35 qualified for analysis. Four patients who received concurrent chemotherapy and RT were analyzed separately. The 31 unilaterally treated patients received a median dose of 47.4 Gy (range, 14.1-68.8 Gy) to the ipsilateral inner ear and 4.2 Gy (range, 0.5-31.3 Gy) to the contralateral inner ear. Hearing loss was associated with the radiation dose received by the inner ear (loss of 210dB was observed in ears receiving >/=45 Gy) and was most appreciable in the higher frequencies (>/=2000 Hz). For a 60-year-old patient with no previous hearing loss in either ear, after receiving 45 Gy, the ipsilateral ear, according to our clinical model, would have a 19.3-dB (95% confidence interval [CI], 15.5-23.0) and 5.4-dB (95% CI, 3.5-7.5) hearing decrement compared with the contralateral ear for 8000 Hz and 1000 Hz, respectively. Age and an initial hearing difference within an ear pair also affected hearing loss. The baseline hearing threshold was inversely related to radiation-induced hearing loss. The degree of hearing loss was dependent on the frequency tested, age, baseline hearing, and baseline difference in hearing between a patient's two ears. CONCLUSION: High-frequency (>/=2000 Hz) hearing acuity worsens significantly after RT in a dose-dependent fashion. A larger number of patients needs to be studied to validate these results. This knowledge can be applied to create guidelines regarding future dose limits to the auditory apparatus for patients undergoing head-and-neck RT.

Normal tissue complication probability modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer.

PURPOSE: To evaluate the ability of a well-known normal tissue complication probability (NTCP) model to predict radiation esophagitis by determining updated model parameters and then comparing these results with the predictive value of other dosimetric parameters. MATERIAL AND METHODS: Clinical and dosimetric data regarding esophagitis were analyzed in 101 inoperable/unresectable non-small-cell lung cancer patients treated by external beam irradiation. Grade 2 or higher esophagitis counted as events. Parameters (TD50, n, and m) of the Lyman normal tissue complication probability (NTCP) model were determined using maximum likelihood analysis, and compared to other dose/volume threshold values including: percentage of esophagus receiving > 40 Gy (V40) to > 75 Gy (V75), and maximum esophageal doses. RESULTS: Sixteen patients developed grade 2-3 acute esophagitis (no G4 or 5). The maximum likelihood analysis produced new Lyman model parameters of: TD50 = 51 Gy, n = 0.44 and m = 0.32. The mean NTCP value is significantly lower (P < 0.001) in the group of patients without esophagitis (13.5%) than with esophagitis (27.2%). The rates of esophagitis are 2.5, 7, 9 and 13.4%, respectively, when the NTCP values are <10%, <15%, <20% and <25%. A significant association is found between esophagitis and dose/volume parameters V40 (P = 0.001) to V70 (P = 0.024). CONCLUSIONS: New values of TD50, n and m offer a good description of the esophagitis distribution in our population. Compared to the use of this model with previously published parameters (associated with late toxicity) predictions of the model for acute esophagitis using the new parameters would indicate that, for a population of patients, the distribution of events as a function of uniform dose would occur with a lower mean uniform dose value (smaller TD50), over a wider range of uniform doses (larger m), while also exhibiting a bigger volume effect (larger n). These new parameter values are supported in essence by the correlations found for the dose/volume threshold parameters.

A placebo-controlled study of fluoxetine in continued treatment of bulimia nervosa after successful acute fluoxetine treatment.

OBJECTIVE: The efficacy of fluoxetine in the acute management of bulimia nervosa is well established; however, few controlled studies have examined whether continuation of pharmacotherapy provides protection from relapse. This study compared the efficacy and safety of treatment with fluoxetine versus placebo in preventing relapse of bulimia nervosa during a 52-week period after successful acute fluoxetine therapy. METHOD: Patients who met DSM-IV criteria for bulimia nervosa, purging type, were assigned to single-blind treatment with 60 mg/day of fluoxetine. After 8 weeks of treatment, patients were considered responders if they experienced a decrease > or =50% from baseline in the frequency of vomiting episodes during 1 of the 2 preceding weeks. Responders were randomly assigned to receive 60 mg/day of fluoxetine or placebo and were monitored for relapse for up to 52 weeks. Patients met relapse criteria if they experienced a return to the baseline vomiting frequency that persisted for 2 consecutive weeks. RESULTS: Of the 232 patients who entered the acute phase, 150 patients (65%) met response criteria and were randomly assigned to receive fluoxetine (N=76) or placebo (N=74). Fluoxetine-treated patients exhibited a longer time to relapse than placebo-treated patients. Quantitative analysis of other efficacy measures, including frequency of vomiting episodes, frequency of binge eating episodes, Clinical Global Impression severity and improvement scores, the patient's global impression score, and Yale-Brown-Cornell Eating Disorder Scale score, indicated that the efficacy of fluoxetine treatment was statistically superior, compared to placebo. There were no clinically relevant differences in safety between groups. Attrition in this study was high, especially in the first 3 months after random assignment to treatment groups. CONCLUSIONS: Continued treatment with fluoxetine in patients with bulimia nervosa who responded to acute treatment with fluoxetine improved outcome and decreased the likelihood of relapse.

The association between presentation PSA and race in two sequential time periods in prostate cancer patients seen at a university hospital and its community affiliates.

PURPOSE: We sought to determine whether African American men diagnosed with prostate cancer in the prostate-specific antigen (PSA) era differed in initial presenting serum PSA levels (iPSA) compared to white men. Recent retrospective studies have demonstrated higher iPSA within the African American men than in white men at the time of diagnosis, suggestive of more advanced disease in African American men. Both biologic differences and/or sociologic factors have been postulated as explaining the noted differences in iPSA. We reviewed our institution's PSA-era experience to determine any association between race and iPSA. MATERIALS AND METHODS: Between January 1990 and September 2001, 4519 patients representing a broad demographic sample were seen in the radiation oncology department of a university hospital or one of its four community affiliates. A total of 2332 eligible patients, with data on race, age, year of diagnosis, Gleason score, T stage, and iPSA, were analyzed. The patients were separated into the two following time periods for analysis, based on the new American Cancer Society screening guidelines: (1) 1991 to 1996 and (2) 1997 to 2001. The relationships between race and iPSA, T stage, Gleason score, and age are explored. RESULTS: Of the 2332 patients analyzed, there were 1968 white men and 364 African American men. For the time period 1990 through 1996, the expected average (median) iPSA level was 10.5 (10.2) and 14.6 (15.8) for white men and African American men, respectively. For 1997 to 2001, the expected average iPSA level was 9.5 (8.4) and 10.8 (9.8), respectively. T stage distributions improved, independent of race, toward earlier stage at presentation. Gleason score distribution remained unchanged. African American men are 2.5-3.1 years younger than white men at diagnosis. CONCLUSIONS: An overall decline in iPSA has occurred in both racial groups over time. More importantly, racial differences in iPSA among men diagnosed in the later time period (1997 to 2001) are less pronounced compared to men diagnosed in the earlier time period (1990 to 1996). This racial convergence in iPSA over time suggests improved penetrance of PSA screening in the African American population. Our findings also suggest that studies comparing racial differences in iPSA should consider time period of diagnosis and possible sociologic changes during that period (i.e., access to medical care, socioeconomic status, and educational level). The American Cancer Society guideline to begin screening African Americans at an earlier age is appropriate.

Prevalence and predictive role of p16 and epidermal growth factor receptor in surgically treated oropharyngeal and oral cavity cancer.

BACKGROUND: The purpose of this study was to describe the relationship of p16 and epidermal growth factor receptor (EGFR) expression with survival in surgically treated patients who had oropharyngeal or oral cavity squamous cell carcinoma (SCC). METHODS: Tissue from 36 patients with oropharyngeal SCC and 49 patients with oral cavity SCC treated between 1997 and 2001 was imbedded and immunostained using a tissue microarray. RESULTS: The p16 was positive in 57% and 13% of patients with oropharyngeal SCC and oral cavity SCC, respectively. EGFR was positive in 60% and 63% of patients with oropharyngeal SCC and oral cavity SCC, respectively. In patients with oropharyngeal SCC, p16 expression was associated with improved disease-specific survival (DSS), overall survival (OS), and time to recurrence (TTR) (p < .01, < .01, and <.01, respectively). EGFR expression was associated with poorer DSS, OS, and TTR (p < .01, = .01, and < .01, respectively). For oropharyngeal SCC, when examining both p16 and EGFR expression as combined biomarkers, high p16 expression coupled with low EGFR expression was associated with improved DSS (p p16 = .01; p EGFR = .01). Patients with oral cavity SCC showed no association between biomarker and outcome. CONCLUSIONS: For patients with oropharyngeal SCC, high p16 and low EGFR were associated with improved outcome, suggesting a predictive role in surgically treated patients.

A phase II study of imatinib in patients with advanced anaplastic thyroid cancer.

BACKGROUND: Currently, there is no standard treatment for metastatic anaplastic thyroid cancer (ATC). DNA microarray analysis has shown platelet-dervived growth factor receptor (PDGFR) overexpression in ATC relative to well-differentiated thyroid cancer. In p53-mutated/deficient ATC cell lines, cABL is overexpressed, and selective inhibition of cABL results in a cytostatic effect. Imatinib inhibits tyrosine kinase activity of Bcr-ABL and PDGF. We hypothesize that patients with ATC that over-expresses PDGF receptors or cABL will respond to imatinib. METHODS: Patients with histologically confirmed ATC who had measurable disease and whose disease expressed PDGF receptors by immunohistochemistry were eligible for study. Imatinib was administered at 400 mg orally twice daily without drug holiday. Response to treatment was assessed every 8 weeks. Patients with complete response, partial responses, or stable disease were treated until disease progression. The study was terminated early due to poor accrual. RESULTS: From February 2004 to May 2007, 11 patients were enrolled and were started on imatinib. At baseline, 4/11 had locoregional disease, 5/11 had distant metastases, and 2/11 had both. Nine of 11 had prior chemoradiation, and 7/11 had thyroidectomy. Eight of 11 were evaluable for response; 4 were excluded for lack of follow-up with radiologic evaluation. The overall response rates at 8 weeks were complete response 0/8, partial response 2/8, and stable disease 4/8. The median time to follow-up was 26 months (ranges 23-30 months). The rate of 6-month progression-free survival was 36% (95% confidence interval, 9%-65%). The rate of 6-month overall survival was 45% (95% confidence interval, 16%-70%). The most common grade 3 toxicity was edema in 25%; other grade 3 toxicities included fatigue and hyponatremia (12.5% each). There were no grade 4 toxicities or treatment related deaths. CONCLUSIONS: Imatinib appears to have activity in advanced ATC and is well tolerated. Due to difficulty of accruing patients with a rare malignancy at a single institution, further investigation of imatinib in ATC may be warranted in a multi-institutional setting.

Outcomes after esophagectomy in patients with prior antireflux or hiatal hernia surgery.

BACKGROUND: Esophagectomy is indicated occasionally for the treatment of patients with refractory gastroesophageal reflux disease (GERD) or recurrent hiatus hernia. The purpose of this study was to evaluate the impact of previous gastroesophageal operations on outcomes after esophagectomy for recurrent GERD or hiatus hernia. METHODS: Using a prospectively accumulated database, a retrospective review was performed to identify patients undergoing esophagectomy for complicated GERD or hiatus hernia. Mortality, perioperative and functional outcomes, and need for reoperation were evaluated, assessing esophagectomy patients who had undergone prior operations for GERD or hiatus hernia. RESULTS: Of 258 patients with GERD or hiatus hernia undergoing esophagectomy, 104 had undergone a previous operation, with a median interval to esophagectomy of 28 months. Transhiatal resection was accomplished in fewer patients undergoing reoperation (87 of 104 versus 151 of 154; p<0.005). A gastric conduit was used as an esophageal replacement in fewer patients with previous operation(s) (89 of 104 versus 150 of 154; p<0.005). Esophagectomy patients with a history of prior gastroesophageal surgery, as compared with those without, sustained more blood loss and were more likely to require reoperation, and fewer reported good to excellent swallowing function (p<0.05). There was no difference in the occurrence of anastomotic leak. CONCLUSIONS: Esophagectomy in patients who have undergone prior operations for either GERD or hiatus hernia can be accomplished without thoracotomy and with satisfactory intermediate-term quality of life. Such patients should be evaluated and prepared for the use of alternative conduits should the remobilized stomach prove to be an unsatisfactory esophageal substitute at the time of esophagectomy.

Thoracodorsal artery scapular tip autogenous transplant: vascularized bone with a long pedicle and flexible soft tissue.

OBJECTIVE: To demonstrate that the 3 reconstructive advantages of the thoracodorsal artery scapular tip transplant (Tdast), a long pedicle, independently mobile tissue components, and the 3-dimensional nature of the scapular tip, will improve the quality and success of complex reconstructions by avoiding vein grafting, preventing the need for 2 separate transplants, and facilitating bony inset. DESIGN: Prospective case series. SETTING: Tertiary care academic medical center. PATIENTS: Twenty-one patients (male to female ratio, 16:5; mean age, 52 years) underwent reconstruction of the upper, middle, and lower face from 2001 through 2006. Indications for reconstruction were tumor ablation in 11 patients, secondary reconstruction in 4 patients, osteoradionecrosis in 4, and posttraumatic reconstruction in 2. Seventeen patients underwent radiation. INTERVENTIONS: All patients underwent harvest of an autogenous transplant of scapular tip bone and latissimus dorsi soft tissue based on the thoracodorsal artery. The mean bone length was 5.2 cm (range, 2.5-9.0 cm), and the mean cutaneous surface area was 68 cm² (range, 20-250 cm²). MAIN OUTCOME MEASURES: Reduction of vein grafting, avoidance of 2 transplants, use of the triangular shape of the scapular tip in reconstruction, complications, and shoulder function. RESULTS: The success rate of transplantation was 100%. The use of this transplant avoided vein grafting in 16 patients and the need for 2 separate transplants in 11 patients, and the 3-dimensional nature of the scapular tip facilitated inset in 13 patients. In 14 patients, more than 1 of these reconstructive advantages was achieved. In 6 patients, all 3 were accomplished. Eleven patients experienced a complication. The major complication rate was 33%, and the minor complication rate was 33%. The mean Constant-Murley test of shoulder function score was 87 of 100 (range, 74-100). CONCLUSIONS: The Tdast is an excellent choice for reconstruction in the head and neck as an alternative to procedures requiring vein grafting and multiple free tissue transplants, or in which the 3-dimensional contour of the scapular tip aids in reconstruction. The complication rate should be assessed in the context of the risk factors of the patient population and the outcome with respect to stable employment, increasing body mass index, and maintenance of shoulder function.

High SEPT9_v1 Expression Is Associated with Poor Clinical Outcomes in Head and Neck Squamous Cell Carcinoma.

The purpose of this work was to determine SEPT9_v1 expression levels in head and neck squamous cell carcinoma (HNSCC) and to analyze whether SEPT9_v1 expression is relevant to clinical outcomes. Recently, the SEPT9 isoform SEPT9_v1 has been implicated in oncogenesis, and methylation of the SEPT9 promoter region was reported in HNSCC. These findings led us to hypothesize that SEPT9_v1 could be differently expressed in HNSCC. To determine whether SEPT9_v1 is expressed in HNSCC, tissue microarray immunohistochemical analysis was performed using a SEPT9_v1-specific antibody. Tissue microarrays stained with a polyclonal SEPT9_v1-specific antibody was used to determine protein expression levels in HNSCC tissue samples, some with known clinical outcomes. This analysis showed that SEPT9_v1 is in fact highly expressed in HNSCC compared with normal epithelium, and high expression levels directly correlated with poor clinical outcomes. Specifically, a high SEPT9_v1 expression was associated with decreased disease-specific survival (P = .012), time to indication of surgery at primary site (P = .008), response to induction chemotherapy (P = .0002), and response to chemotherapy (P = .02), as well as advanced tumor stage (P = .012) and N stage (P = .0014). The expression of SEPT9_v1 was also strongly correlated with smoking status (P = .00094). SEPT9_v1 is highly expressed in HNSCC, and a high expression of SEPT9_v1 is associated with poor clinical outcomes. These data indicate that SEPT9_v1 warrants additional investigation as a potential biomarker for HNSCC.

Chemotherapy alone for organ preservation in advanced laryngeal cancer.

BACKGROUND: For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy. METHODS: Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response. RESULTS: A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively. CONCLUSION: Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site.

Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence.

PURPOSE: The goal of this study was to examine the effect of tobacco use on disease recurrence (local/regional recurrence, distant metastasis, or second primary) among patients with human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP) following a complete response to chemoradiation therapy. EXPERIMENTAL DESIGN: Between 1999 and 2007, 124 patients with advanced SCCOP (86% with stage IV) and adequate tumor tissue for HPV analysis who were enrolled in one of two consecutive University of Michigan treatment protocols were prospectively included in this study. Patients were categorized as never-, former, or current tobacco users. The primary end points were risk of disease recurrence and time to recurrence; secondary end points were disease-specific survival and overall survival. RESULTS: One hundred and two patients (82.3%) had HPV-positive tumors. Over two thirds (68%) of patients with HPV-positive tumors were tobacco users. Among HPV-positive patients, current tobacco users were at significantly higher risk of disease recurrence than never-tobacco users (hazard ratio, 5.2; confidence interval, 1.1-24.4; P = 0.038). Thirty-five percent of HPV-positive ever tobacco users recurred compared with only 6% of HPV-positive never users and 50% of HPV-negative patients. All HPV-negative patients were tobacco users and had significantly shorter times to recurrence (P = 0.002), and had reduced disease-specific survival (P = 0.004) and overall survival (P < 0.001) compared with HPV-positive patients. Compared with HPV-positive never-tobacco users, those with a tobacco history showed a trend for reduced disease-specific survival (P = 0.064) but not overall survival (P = 0.221). CONCLUSIONS: Current tobacco users with advanced, HPV-positive SCCOP are at higher risk of disease recurrence compared with never-tobacco users.

Advanced squamous cell carcinoma of the oropharynx: efficacy of positron emission tomography and computed tomography for determining primary tumor response during induction chemotherapy.

BACKGROUND: To evaluate the efficacy of fluorine-18-fluorodeoxyglucose emission tomography (FDG-PET) and CT versus endoscopy with biopsy under general anesthesia for estimating tumor volume reduction among patients treated with induction chemotherapy for advanced squamous cell carcinoma (SCC) of the oropharynx. METHODS: Twelve patients with oropharyngeal SCC nested in a phase II, induction chemoradiation, organ preservation trial (University of Michigan Cancer Center 9921) underwent tumor volume reduction estimation as assessed by FDG-PET, CT, and endoscopy with biopsy. RESULTS: In 9 of 12 patients, FDG-PET, CT, and endoscopy demonstrated agreement in estimation of tumor reduction. Two patients had discordant results, whereas 1 patient was inadequately evaluated with FDG-PET. The kappa value for PET versus endoscopy was 0.62, which is categorized as substantial agreement. The kappa value for CT versus endoscopy was 0.40, which is categorized as fair agreement. CONCLUSION: FDG-PET may be as efficacious as endoscopy with biopsy under general anesthesia for estimating tumor volume reduction with induction chemotherapy.

Chemoselection as a strategy for organ preservation in patients with T4 laryngeal squamous cell carcinoma with cartilage invasion.

OBJECTIVES/HYPOTHESIS: High rates of overall survival (OS) and laryngeal preservation were achieved in two sequential phase II clinical trials in patients with stage III/IV laryngeal squamous cell carcinoma (SCC). Patients were treated with chemoradiation after a >50% primary tumor response to one cycle of neoadjuvant chemotherapy (IC). We analyzed outcomes for T4 patients with cartilage invasion from both studies. STUDY DESIGN: Retrospective. METHODS: Records from 36 patients with T4 SCC of the larynx with cartilage invasion alone (n = 16) or cartilage invasion and extralaryngeal spread (n = 20) were retrospectively reviewed. All were treated with one cycle of cisplatin (100 mg/m(2)) [or carboplatin (AUC 6)] and 5-fluorouracil (1,000 mg/m(2)/d for 5 days) (P+5FU). Those achieving >50% response at the primary tumor received chemoradiation (70 Gy; 35 fractions with concurrent cisplatin-100 mg/m(2) [carboplatin (AUC 6)] every 21 days for 3 cycles), followed by adjuvant P+5FU for complete histologic responders (CHR). Patients with <50% response after IC underwent total laryngectomy and postoperative radiation. RESULTS: Twenty-nine of 36 patients (81%) had >50% response following IC. Of these, 27 received definitive chemoradiation, 23 (85%) obtained CHR, with 58% laryngeal preservation rate. The 3-year OS was 78%, and the disease-specific survival was 80% (median follow-up 69 months). Following chemoradiation, 8/11 (73%) patients with an intact larynx had >75% understandable speech, 6/36 (17%) were g-tube dependent and 6/36 (17%) were tracheostomy dependent. CONCLUSIONS: Our results suggest that chemo-selection is a feasible organ preservation alternative to total laryngectomy for patients with T4 laryngeal SCC with cartilage invasion.