Introduction As traditional measures such as overall survival (OS) or disease-free survival (DFS) alone do not give a holistic view of the outcomes of a treatment paradigm, we determine to add the evidence of quality-adjusted life year (QALY) and disability-adjusted life year (DALY) to the outcomes of the nasopharyngeal carcinoma patients (NCP) treated with definitive chemoradiation therapy (chemoRT) with or without induction chemotherapy (induction chemo). Methods This is a retrospective analysis of 85 NCPs treated at an academic state institution. The OS estimated by the Kaplan-Meier method and the multivariate Cox regression model determined the co-variables associated with the OS. The relationship between QALYs gained and DALYs saved were calculated from age of the disease onset, duration of the disease, quality of life (QoL) and disability weights. Results Of the 85 eligible NCPs of this cohort, the disease frequency distribution per the World Health Organization (WHO) classification was 41.2% for Type-I, 42.4% for Type-II, and 16.5% for Type-I II. The median follow-up (24 months). The five-year OS of patients treated with concurrent chemoRT vs. induction chemo followed by concurrent chemoRT was 54.7 vs. 14.8% for WHO Type I, 60.1 vs. 58.3% for WHO Type II, and 83.3 vs. 50.0% for WHO Type III (p=0.029). The average DALYs saved with concurrent chemoRT were 12.2 years vs. 5 years for induction chemo followed by concurrent chemoRT. The average QALYs gained with concurrent chemoRT were 6.9 years vs. 3.1 years for induction chemo followed by concurrent chemoRT. Conclusion Patients treated with concurrent chemoRT had an increased QoL when compared to induction chemo followed by concurrent chemoRT. The average DALYs saved were higher in the patients treated with concurrent chemoRT than treated with induction chemo followed by concurrent chemoRT.

For Patients with T4 laryngeal cancer, surgery is usually followed by adjuvant radiotherapy (RT) to improve local or regional control and distant metastasis rates. We decided to test the hypothesis that adjuvant RT improves the disease free survival (DFS), overall survival (OS), and local or regional control more in patients with shorter intervals between surgery and RT compared to that of patients treated with longer intervals. To assess whether the time interval between surgery followed by adjuvant RT determines the clinical outcomes in T4 laryngeal cancer patients (T4LCPs). This is a retrospective analysis of 112 T4LCPs who underwent laryngectomy (surgery) followed by adjuvant RT with different time intervals (4 to 10 weeks) at an academic state institution. Correlation of survival with several treatment duration interval parameters were evaluated. The OS and DFS were estimated by using Kaplan–Meier method. The significance of survival variables were analyzed using the Cox univariate and multivariate proportional hazards model. A p value of less than 0.05 was considered statistically significant. The SPSS 24.0 software was used for data analysis. The baseline characteristics of all 112 T4LCPs were measured with median follow up of 31 months. Our results indicated a higher survival rates in T4LCPs who were treated by RT shortly after surgery compared with T4LCPs treated by RT with prolonged duration (p=0.013) and negatively correlated with the time interval indicating that the early start of RT after surgery increased the survival outcomes. There was a trend for improved loco regional control (p=0.038) and fewer distant metastasis (p= 0.038) in T4LCPs treated within short duration compared with long intervals indicating a statistically significant DFS (p=0.030). Age is the only factor that affected the clinical outcome in the multivariate Cox regression analysis (p=0.015) with a statistically significant OS (p=0.041). The NCCN guidelines recommend laryngectomy with or without RT as the primary treatment modality for all advanced laryngeal cancers. Our report indicates that OS and DFS among patients undergoing surgery followed by adjuvant RT with a shorter intervals between surgery and RT to be superior to that of the patients treated with longer intervals.

Racial differences in clinical outcomes among laryngeal cancer patients have been reported and Black American patients appear to have worse survival compared to White Americans. However, there are not many studies looking at the potential racial differences in outcomes in T1 Glottic cancers. One of the hypotheses underlying racial differences in clinical outcomes is lack of adequate access to healthcare for the Blacks. Thus, the Blacks may present with more advanced stages at the time of diagnosis, thus leading to poorer outcomes. We hypothesized that since T1 glottic cancer is one of the earliest stages, with the least tumor burden, outcomes should be similar between the two races. At our institution, a safety-net academic medical center, there are no differences in the treatment being given Blacks or Whites, stage-for-stage. To our surprise, we found poorer clinical outcomes for the blacks. What we report here is a hypothesis generating analysis. To evaluate the impact of race (Black vs. White) on the outcome of T1 glottic squamous cell carcinoma (SCCa) in patients treated with radiation therapy (RT) alone. Between 2002 and 2018, twenty-five (37.3%) Black patients and forty-two (62.7%) White patients with T1 glottic SCCa underwent RT in our academic state institution. Chi- square test, Kaplan- Meier method, and Cox regression models were used to assess for racial influence; p-values less than 0.05 were considered statistically significant. The SPSS 24.0 software was used for data analyses. The baseline characteristics of all 67 T1 glottic SCCa patients documented. The median follow-up duration was 51 months (range, 0-266 months). Black patients (n=14; 20.9%) and White patients (n=28; 41.8%) were treated with a conventional schedule (CONV) 2 Gy/ day; total dose 66 Gy/ 7 weeks. Eleven Black patients (16.4%) and White patients (n=14; 20.9%) were treated in a hypo-fractionated (HYPO) schedule 2.25 Gy/ day; total dose 63 Gy/5 weeks. The 5-year overall survival (OS) for Blacks vs. Whites treated with CONV was 51.6 vs. 66.0% (p= 0.001). For those treated with HYPO, the OS was 85.7 vs. 99.6% (p= 0.001). The 5- year local relapse free survival (LRPS) for Blacks vs. Whites treated with CONV was 34.1 vs. 40.9% (p= 0.163) and for those treated with HYPO was 42.6 vs. 72.7% (p= 0.163), showing no statistical significance between the two groups. In the univariate Cox regression analysis, the covariates of ethnicity, RT type, voice-hoarseness, gender, and type of insurance were statistically significant with p-value less than 0.05. However, in the multivariate Cox regression analysis only, the co-variates of ethnicity-Black (HR, 4.39; 95% CI, 1.46-13.17; p=0.008), RT type-CONV (HR, 20.82; 95% CI, 3.63-119.32; p=0.001), voice-hoarseness (HR, 3.80; 95% CI, 1.26-11.41; p=0.017), and gender-male (HR, 7.08; 95% CI, 1.46-34.22; p=0.015) were statistically significant. Race appears to be an independent prognostic factor for OS in T1 glottic cancers. Although local control rates were poorer for Blacks, it didn’t reach statistical significance.

Abstract Purpose: To assess the prognostic significance of tumor HPV/p16 status among oropharyngeal squamous-cell carcinoma (SCC) patients. Methods: A retrospective analysis of 80 patients diagnosed with oropharyngeal SCC between 2008 and 2018 at an academic medical center with known HPV/p16 status was performed. Pearson’s Chi-squared test was used to compare the proportional differences between the known tumor HPV status among positive and negative p16 staining groups. Kaplan- Meier analysis was used to estimate overall survival [OS] and local control [LC] between the HPV groups stratified by risk and compared using the log-rank test. Uni and multi-variable Cox hazard regression analyses were used to compare the risk of death among patients with HPV- positive and HPV- negative cancer. The SPSS v.24.0 was used for all statistical analyses. Results: Our patient cohort included 37.5% HPV- positive and 62.5% HPV-negative (median age, 61 y; range 45-86 y) patients. Patient groups were classified on the basis of risk factors: HPV/p16 status, pack-years [py] of tobacco smoking, and tumor stage into low (p16+, ≤ 10 py), intermediate (p16+, > 10 py/p16-, < 10 py), and high risk (p16-, > 10 py/ any T4), accounting for 36.7%, 36.7% and 26.7% of HPV-positive and 0%, 20% and 40% of HPV-negative patients, respectively (p=0.000). The median follow-up duration for this cohort was 34 months (range 0 to 154 months). The low risk HPV-positive group had better 5-year OS rates (87.5%, vs. 59.5% and 27.2%) compared to intermediate and high risk groups (p=0.003 by the log-rank test). After adjustment for gender, age, race, income level, distance travelled, tobacco exposure, alcohol history, tumor stage, and treatment modality, this group had a 63% reduction in the risk of death (hazard ratio, 0.37; 95% CI, 0.18-0.77; p= 0.008). Insurance and BMI was associated with a 71% reduction (hazard ratio, 0.29; 95% CI, 0.97-0.89; p=0.032), and a 49% reduction in the risk of death (hazard ratio, 0.51; 95% CI, 0.37-0.71; p=0.000), respectively. In terms of LC, the low risk HPV-positive patients had better 3-year rates 70.1%, vs. 55.7% and 39.9% compared to the intermediate and, high risk groups (p=0.379). Conclusion: Tumor HPV/p16 status may be an independent prognostic factor along with insurance status and BMI for overall survival among oropharyngeal SCC patients. Citation Format: Mary R. Nittala, Eswar K. Mundra, Ashley Albert, William C. Woods, Maria L. Smith, Robert D. Hamilton, Lana Jackson, Gina Jefferson, Satyaseelan Packianathan, Eldrin Bhanat, Varsha Manucha, Srinivasan Vijayakumar. Univariate and multivariate prognostic factors for overall survival among oropharyngeal cancer patients with known HPV/p16 status [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-232.

Abstract Purpose: To evaluate the impact of race (African-American [AA] vs. Caucasians [C]) on the survival outcome in patients with oropharyngeal squamous-cell carcinoma (SCC) known HPV/p16 status. Methods: Between 2008 and 2018, eighty patients with known HPV/p16 status were diagnosed with oropharyngeal SCC in our academic state institution. Chi-square test, Kaplan-Meier method, and Cox regression models were used to assess for racial influence; p-values less than 0.05 were considered statistically significant. The SPSS v.24.0 was used for all statistical analyses. Results: The median follow-up duration was 34 months (range 0 to 154 months). Our patient cohort included 48.8% AA and 51.2% C (median age, 61 y; range 45-86 y) patients. Patient risk groups were stratified based on HPV/p16 status, pack-years [py] of tobacco smoking, and tumor stage into low (p16+, ≤10 py), intermediate (p16+, >10 py/p16-, <10 py), and high risk (p16-, >10 py/ any T4), accounting for 2.6%, 25.6% and 71.8% of AA vs. 24.4%, 26.8% and 48.8% of C patients, respectively (p=0.013). The C patients had better 5-year overall survival [OS] rates (88.9%, 62.2% and 37.5% vs. na, 48.0% and 25.6% compared to AA patients stratified by risk (p=0.009). The OS of low risk AA patients was not assessable because of a low number (1) of patients in that group. In the bivariate Cox regression analysis, the covariates stratified by race, type of insurance, BMI level, HPV/p16 status, risk groups, and 8th AJCC staging were statistically significant with p-value less than 0.05. In the multivariate analysis, the covariates of insurance-private was associated with 87% reduction (hazard ratio, 0.13; 95% CI, 0.03-0.61; p=0.010), insurance-Medicare was associated with 71% reduction (hazard ratio, 0.29; 95% CI, 0.11-0.74; p=0.010), and AJCC TNM stages III, IV and IVB (98%, 97% and 93%) with reduction in the risk of death (hazard ratio, 0.02; 95% CI, 0.00-0.38; p=0.009), (hazard ratio, 0.03; 95 CI, 0.00-0.55; p=0.017), (hazard ratio, 0.07; 95% CI, 0.00-0.92), respectively. In terms of local control [LC], the C patients also had better 3-year rates 66.4%, vs. 32.8% compared to AA patients (p=0.049). Conclusion: In our patient population, race appears to be an independent prognostic factor for OS and LC in oropharyngeal SCC patients with known HPV/p16 status. Citation Format: Mary R. Nittala, Eswar K. Mundra, Maurice L. King, Ashley Albert, Williams C. Woods, Maria L. Smith, Robert D. Hamilton, Lana Jackson, Gina Jefferson, Satyaseelan Packianathan, Varsha Manucha, Srinivasan Vijayakumar. Impact of race on outcomes in oropharyngeal squamous-cell carcinoma patients with known HPV/p16 status [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-104.

The purpose of this study was to present the outcomes of oropharyngeal cancers treated with intensity‐modulated radiotherapy (IMRT) especially the differences between tonsillar and base of tongue (BOT) primaries.

The Ewing's sarcoma family of tumors (EFTs) are a rare subtype of tumor that include primitive neuroectodermal tumors (PNETs), typical Ewing's sarcoma, and atypical Ewing sarcoma. EFTs of the hand are extremely rare, and none have been reported to our knowledge beyond the fifth decade of life.1-3 EFTs present most frequently in the second decade of life and have a male predominance.3 Multimodality therapy is typically used to treat patients.

To study the differences in presentation between tonsil and base of tongue primaries and to evaluate the outcomes based on the primary site and initial stage at presentation. A retrospective analysis was performed on 125 patients with biopsy proven squamous cell carcinomas of oropharynx, treated at our institution between the years 2008 and 2015. We studied the difference in the initial stage at presentation based on primary site of disease tonsil vs. base of tongue and evaluated the outcomes including loco-regional failure, distant metastases, disease free survival and overall survival. Statistics: We analyzed cumulative incidence of events between the groups using Gray's test. Among 125 patients, 77 with tonsil primary and 48 with base of tongue. Nodal metastases at initial presentation, grouped into N0, 1,2a vs. N2b vs. N2c, N3.64.9% of tonsillar primaries presented with T1-2 and 35% with T3-4 at diagnosis. 41.6% of base of tongue primaries, presented with T1-2 and 58.3% with T3-4 at diagnosis. Fifty-four percent of base of tongue primaries, initially presented with advanced nodal stages N2c or higher compared to 30% of tonsillar primaries. Median radiation dose was 70 Gy delivered utilizing IMRT technique and median follow up duration was 2 years. At 2 years, the cumulative incidences of loco regional recurrences were 8% in both tonsil and base of tongue groups (P = 0.76). However, the cumulative incidence of distant metastases at 2 years were 8% in tonsil group vs. 26% in base of tongue (P = 0.009). The incidence of distant metastases, especially higher in patients with ≥N2c nodal disease, 21.7% in tonsil vs. 54.1% in base of tongue group. At 2 years there was no statistically significant difference in overall survival (73% vs. 75%) as well as Disease free survival (64% vs. 54%) between both tonsil and base of tongue groups. (1) Intensity modulated radiation therapy concurrently with chemotherapy result in a high local control rate (92% at 2 years) for both tonsil and base of tongue primary lesions. (2) Base of tongue is associated with a higher risk of distant metastases compared to the tonsil primaries. (3) The incidence of distant metastases is consistently high in base of tongue primaries for all nodal stages (N0, 1,2a vs. N2b vs. N2c, 3). (4) Patients with N2c are at a high risk of developing distant metastases and other therapies such as neoadjuvant chemotherapy should be considered.Tabled 1Abstract 2958; Table 1.TonsilBOTTotal Number7748N0,1,2a26/77 (33.76%)10/48(20.83%)Distant Mets0%10%N2b28/77(36.36%)12/48(25%)Distant Mets3.6%16.1%N2c+N323/77(30%)26/48(54.16%)Distant Mets21.7%54.1%Cumulative Incidence of Local+Regional recurrence at 2 years8%8%, P = 0.76Cumulative Incidence of Distant metastases at 2 years8%26%, P = 0.009 Open table in a new tab

Purpose/Objective(s)Advanced squamous cell carcinomas (SCE) of the head and neck are usually treated with concurrent chemotherapy. We reviewed the experience at our institution using concurrent chemotherapy and radiation therapy (RT) for advanced squamous cell cancers to assess which chemotherapy is optimal for use in such a regimen.Materials/MethodsPoster Viewing Abstracts 2759; Table 1Cetuximab (N=36)Low Dose Cisplatin (N=36)High Dose Cisplatin (N=15)Tis0 (0%)2 (6%)0 (0%)T1/T226 (14%)12 (3%)8 (7%)T36 (17%)16 (46%)4 (27%)T44 (11%)5 (14%)3 (20%)N05 (14%)15 (43%)4 (27%)N19 (25%)5 (14%)2 (13%)N222 (61%)12 (34%)8 (53%)N30 (0%)3 (9%)1 (7%) Open table in a new tab ResultsThe overall local recurrence rates were 3% in LDC, 0% in C, and 22% in CX groups (P=.02). Regional recurrence rates were 25% in LDC, 8% in C, and 20% in CX (P=.18). The distant metastasis rates were 14% in LDC, 20% in C and 11% in CX (P=.66). Overall median survival was 2.2 years for high dose cisplatin, 2.8 years for cetuximab and has not been reached for weekly cisplatin. Cetuximab had lower grade 3 or 4 toxicity (5.7%) compared to weekly cisplatin (16.7%) or high dose cisplatin (26.7%) (P=.107). The hazard ratios for risk of death were 2.73, favoring low dose cisplatin over cetuximab (P=.096), and 3.48, favoring low dose cisplatin over high dose cisplatin (P=.065). Hazard ratio for death for cetuximab compared to high dose cisplatin is 1.27, slightly favoring Cetuximab (P=.668).ConclusionSeveral regimens have been used in combination with RT for advanced squamous cell cancers of the head and neck. In our experience, low dose cisplatin is superior to cetuximab for locoregional control and survival. The toxicity patterns are different but we did not note significant grade III/IV toxicities. A recent published trial comparing cisplatin and panitumumab, another EGFR inhibitor, also showed that cisplatin was superior (CONCERT-2 trial). We conclude low dose cisplatin should be the drug of choice to be combined concurrently with radiation therapy for advance SCE of the head and neck. If the patient cannot receive cisplatin, then cetuximab is a reasonable alternative. Purpose/Objective(s)Advanced squamous cell carcinomas (SCE) of the head and neck are usually treated with concurrent chemotherapy. We reviewed the experience at our institution using concurrent chemotherapy and radiation therapy (RT) for advanced squamous cell cancers to assess which chemotherapy is optimal for use in such a regimen. Advanced squamous cell carcinomas (SCE) of the head and neck are usually treated with concurrent chemotherapy. We reviewed the experience at our institution using concurrent chemotherapy and radiation therapy (RT) for advanced squamous cell cancers to assess which chemotherapy is optimal for use in such a regimen. Materials/MethodsPoster Viewing Abstracts 2759; Table 1Cetuximab (N=36)Low Dose Cisplatin (N=36)High Dose Cisplatin (N=15)Tis0 (0%)2 (6%)0 (0%)T1/T226 (14%)12 (3%)8 (7%)T36 (17%)16 (46%)4 (27%)T44 (11%)5 (14%)3 (20%)N05 (14%)15 (43%)4 (27%)N19 (25%)5 (14%)2 (13%)N222 (61%)12 (34%)8 (53%)N30 (0%)3 (9%)1 (7%) Open table in a new tab ResultsThe overall local recurrence rates were 3% in LDC, 0% in C, and 22% in CX groups (P=.02). Regional recurrence rates were 25% in LDC, 8% in C, and 20% in CX (P=.18). The distant metastasis rates were 14% in LDC, 20% in C and 11% in CX (P=.66). Overall median survival was 2.2 years for high dose cisplatin, 2.8 years for cetuximab and has not been reached for weekly cisplatin. Cetuximab had lower grade 3 or 4 toxicity (5.7%) compared to weekly cisplatin (16.7%) or high dose cisplatin (26.7%) (P=.107). The hazard ratios for risk of death were 2.73, favoring low dose cisplatin over cetuximab (P=.096), and 3.48, favoring low dose cisplatin over high dose cisplatin (P=.065). Hazard ratio for death for cetuximab compared to high dose cisplatin is 1.27, slightly favoring Cetuximab (P=.668). The overall local recurrence rates were 3% in LDC, 0% in C, and 22% in CX groups (P=.02). Regional recurrence rates were 25% in LDC, 8% in C, and 20% in CX (P=.18). The distant metastasis rates were 14% in LDC, 20% in C and 11% in CX (P=.66). Overall median survival was 2.2 years for high dose cisplatin, 2.8 years for cetuximab and has not been reached for weekly cisplatin. Cetuximab had lower grade 3 or 4 toxicity (5.7%) compared to weekly cisplatin (16.7%) or high dose cisplatin (26.7%) (P=.107). The hazard ratios for risk of death were 2.73, favoring low dose cisplatin over cetuximab (P=.096), and 3.48, favoring low dose cisplatin over high dose cisplatin (P=.065). Hazard ratio for death for cetuximab compared to high dose cisplatin is 1.27, slightly favoring Cetuximab (P=.668). ConclusionSeveral regimens have been used in combination with RT for advanced squamous cell cancers of the head and neck. In our experience, low dose cisplatin is superior to cetuximab for locoregional control and survival. The toxicity patterns are different but we did not note significant grade III/IV toxicities. A recent published trial comparing cisplatin and panitumumab, another EGFR inhibitor, also showed that cisplatin was superior (CONCERT-2 trial). We conclude low dose cisplatin should be the drug of choice to be combined concurrently with radiation therapy for advance SCE of the head and neck. If the patient cannot receive cisplatin, then cetuximab is a reasonable alternative. Several regimens have been used in combination with RT for advanced squamous cell cancers of the head and neck. In our experience, low dose cisplatin is superior to cetuximab for locoregional control and survival. The toxicity patterns are different but we did not note significant grade III/IV toxicities. A recent published trial comparing cisplatin and panitumumab, another EGFR inhibitor, also showed that cisplatin was superior (CONCERT-2 trial). We conclude low dose cisplatin should be the drug of choice to be combined concurrently with radiation therapy for advance SCE of the head and neck. If the patient cannot receive cisplatin, then cetuximab is a reasonable alternative.

To compare outcomes and toxicities between Cetuximab vs Cisplatin concurrently with intensity modulated radiation therapy in locally advanced squamous cell carcinomas of the Head and Neck. We retrospectively reviewed 126 patients with biopsy proven squamous cell carcinomas of the head and neck that were treated with Intensity Modulated Radiation therapy concurrently with either weekly Cisplatin or weekly Cetuximab. All patients were treated at our Institute between 2005 and 2011. Toxicity due to treatment was scored using RTOG toxicity scale. Statistics: Differences between patterns and treatment groups were analyzed using Fisher’s Exact test. Among 126 patients, 66 patients were treated with Cetuximab and 57 with Cisplatin concurrently with radiation therapy. Median age at diagnosis was 53 years. Site of primary was Oral Cavity in 13, Oropharynx-47, Larynx-38, Hypopharynx-5, Nasopharynx-4, PNS-6 and Miscellaneous-10. Median radiation dose was 70 Gy (range 60-70 Gy). Among 66 patients in the Cetuximab+RT group, 36 patients developed skin rash (54.54% ). With a median follow up of 36 months, the loco regional (LR) control was 74% for all patients. Loco-regional control was 70% in the Cetuximab+RT group and 79% in the Cisplatin+RT group, with no statistically significant difference. 3 year Overall Survival for the entire group was 64.22%, for Cetuximab+RT group 63.63% and for the Cisplatin+RT group was 64.91%. In addition, 2 year Relapse free survival was 41% in the Cetuximab+RT group and 49.1% in the Cisplatin+RT group. Cetuximab being considered as a less toxic alternative to Cisplatin concurrently with radiation therapy, particularly for those patients not medically fit for Cisplatin. RTOG open trial 1016, compares Cisplatin vs Cetuximab, in HPV positive oropharyngeal patients. Our results showed that there were no difference in patterns of failure, relapse free and overall survivals between Cetuximab+RT group vs Cisplatin+RT group. In the Cetuximab+RT group Skin rash was observed in 54% of patients. Pharyngitis was observed, 8.7% in the Cisplatin+RT group and none in the Cetuximab+RT group (p = 0.011). No statistically significant differences in the remaining treatment related toxicities. Our retrospective study results showed that Cetuximab and Cisplatin were equally efficacious, but with a slightly different toxicity profiles.Scientific Abstract 2999; TablePatterns of Failure, Survival and Toxicities between Cetuximab+RT and Cisplatin+RT GroupsCetuximab+RTCisplatin+RTP valuePatterns of FailureLoco Regional Failure20/66 (30.03%)12/57 (21.05%).304Distant Failure7/66 (10.6%)10/57 (17.54%).303Survival3 year OS63.63 %64.91 %NSHematological Toxicity:RTOG Grade 2 & 3Platelets0 (0%)4 (7.01%).082Neutrophils2 (3.03%)4 (7.01%).62Hemoglobin6 (9.09%)7 (12.28%).315Radiation Toxicity:RTOG Grade 2 & 3Skin18 (27.27%)12 (21.05%).398Mucous Membrane24 (36.36%)19 (33.33%).999Pharynx0 (0%)5 (8.77%).011 Open table in a new tab

In 2014, more than 40,000 people in the United States will be diagnosed with head and neck squamous cell cancer (HNSCC) and nearly 8400 people will die of the disease (www.cancer.org/acs/groups). Little is known regarding molecular targets that might lead to better therapies and improved outcomes for these patients. The incorporation of taxanes into the standard cisplatin/5-fluouracil initial chemotherapy for HNSCC has been associated with improved response rate and survival. Taxanes target the β-subunit of the tubulin heterodimers, the major protein in microtubules, and halt cell division at G2/M phase. Both laboratory and clinical research suggest a link between β-tubulin expression and cancer patient survival, indicating that patterns of expression for β-tubulin isotypes along with activity of tumor suppressors such as p53 or micro-RNAs could be useful prognostic biomarkers and could suggest therapeutic targets. © 2014 Wiley Periodicals, Inc.

PURPOSE:To determine if computed tomographic (CT) texture and histogram analysis measurements of the primary mass are independently associated with overall survival in patients with locally advanced squamous cell carcinoma of the head and neck who were previously treated with cisplatin, 5-fluorouracil, and docetaxel (TPF) induction chemotherapy.MATERIALS AND METHODS:This institutional review board-approved retrospective study included 72 patients with locally advanced squamous cell carcinoma of the head and neck who were treated with induction TPF chemotherapy in 2004-2010. CT texture and histogram analysis of the primary mass on the pretherapy CT images were performed by using TexRAD software before and after application of spatial filters at different anatomic scales ranging from fine detail to coarse features. Cox proportional hazards models were used to examine the association between overall survival and the baseline CT imaging measurements and clinical variables.RESULTS:Primary mass entropy and skewness measurements with multiple spatial filters were associated with overall survival. Multivariate Cox regression analysis incorporating clinical and imaging variables indicated that primary mass size (hazard ratio [HR], 1.58 for each 1-cm increase; P = .018), N stage (HR, 8.77 for N3 vs N0 or N1; P = .002; HR, 4.99 for N3 vs N2; P = .001), and primary mass entropy (HR, 2.10 for each 0.5-unit increase; P = .036) and skewness (HR, 3.67 for each 1.0-unit increase; P = .009) measurements with the 1.0 spatial filter were independently associated with overall survival.CONCLUSION:Independent of tumor size, N stage, and other clinical variables, primary mass CT texture and histogram analysis parameters are associated with overall survival in patients with locally advanced squamous cell carcinoma of the head and neck who were treated with induction TPF. Online supplemental material is available for this article.

Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP) who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

To study the correlation between the presences of necrosis in cervical lymph nodes based on pre-operative CT scans in patients with head and neck malignancies to extra capsular extension on post-operative pathology. We retrospectively studied 33 patients with proven head and neck malignancies that underwent neck dissection as part of definitive treatment, without receiving any neo-adjuvant chemotherapy. In case of multiple nodes we have taken into consideration of the largest node with necrosis. Statistical Methods To examine correlations between variables, Spearman correlation coefficients were constructed. Fisher's exact tests were used to examine relationships between categorical variables. Out of a total of 33 patients, 17 had necrosis (Group 1) on the pre-operative CT scans and 16 were without necrosis (Group 2). Based on the post-op pathology, 14 had ECE in the necrosis group (82%) compared to 7 in the non-necrosis group (44%), which is statistically significant (p = 0.021). We also analyzed the patients having maximum diameter of the nodes <3 cm (31 pts.). Again, 86% were found to have ECE in necrosis group (Group 3) compared to 47% in the non-necrosis group (Group 4), with statistical significance (p = 0.027). All the patients with ECE received adjuvant chemoradiation treatment. Median follow-up in this study was 11.6 months. The entire patient in this study was alive except one died due to co-morbidities. The recurrence rate was 25% (4/16) in the non-necrosis group and 18% (3/17) in the necrosis group. Presence of necrosis on the pre op CT scans shows high correlation with extra capsular extension on post-operative pathology, even in neck nodes <3 cm. Studies have shown that extracapsular extension is the single most important risk factor that predicts loco-regional recurrence (Peters et al), and therefore is usually treated with of adjuvant chemo radiation therapy (Bernier et al). Predicting ECE upfront before the surgery may help clinicians in determining the course of treatment in addition to the primary site and stage of the disease.Poster Viewing Abstract 2726; TableECE(+)ECE(−)P valueAll nodes Group 1Necrosis(+)14/17 (82.35%)3/17 (17.64%).021 Group 2Necrosis(−)7/16 (43.75%)9/16 (51.25%)Nodes <3 cm Group 3Necrosis(+)12/14 (85.71%)2/14 (14.28%).027 Group 4Necrosis(−)7/15 (46.66%)8/15 (53.34%)Abbreviation: ECE = extracapsular extension, + = positive, − = negative. Open table in a new tab

INTRODUCTION Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. CASE REPORT A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 × 3 × 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725–891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. CONCLUSION Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

Objectives:In this retrospective study we evaluate the tolerability and outcomes after induction chemotherapy for patients with predominately low socioeconomic status (SES) with locally advanced head and neck cancer (LAHNC). Methods:One hundred eighteen patients with LAHNC of the hypopharynx, larynx, oral cavity, or oropharynx began curative intent therapy with induction cisplatin (75 or 100 mg/m2), docetaxel (75 mg/m2), and 5-fluorouracil (750 mg/m2×5 d or 1000 mg/m2×4 d; continuous infusion) every 3 weeks (DPF) for a planned 2 to 3 cycles. All patients were to receive curative radiotherapy with concurrent systemic therapy. Associations were tested using &khgr;2 test, and survival estimates were calculated using the Kaplan-Meier method. Results:Most patients (75.4%) were of low SES. Induction DPF was delivered for a median of 2 cycles (range, 1 to 3) and 14% of the patients (n=17) died during induction DPF. After DPF, 38.2% of patients were unable to complete or receive planned definitive therapy. Overall 15.3% of patients died during therapy, and mortality was associated with a Karnofsky performance status <80 (P=0.04). At 2 years the locoregional control was 52.7%, whereas the distant metastases free rate was 72.6%, and the overall survival rate was 34.1%. Low SES patients were less likely to achieve locoregional control (P=0.05) or survive (P=0.08). Conclusions:In this population of LAHNC patients of low SES with a high tumor burden and poor performance status, use of induction DPF was associated with 15.3% mortality during therapy and precluded 38.2% of patients from initiating or completing planned definitive therapy.