Aims Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Methods Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Results Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). Conclusions White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy.

Abstract Background: Chemotherapy can affect circulating immune cells. Low lymphocyte counts have been associated with worse prognosis in many cancers and inferior responses to immune checkpoint therapy. The effects of neoadjuvant chemotherapy on the immune system and its association with clinical outcomes in breast cancer is not well described. Methods: A database was constructed of patients diagnosed with early stage triple negative breast cancer (TNBC) treated with neoadjuvant chemotherapy. Clinicopathologic information was extracted from the local electronic tumor registry or by chart review. Circulating lymphocyte and monocyte counts were assessed at the time of diagnosis, after neoadjuvant chemotherapy, and prior to surgery (all values in K/cu mm). These were correlated with clinicopathologic data, pathologic complete response (pCR) rates, and disease free survival (DFS) using rank sum test and Spearman correlation, t-test and log rank test, respectively. Results: From 2000-2015, 426 patients with breast cancer treated with neoadjuvant chemotherapy were sequentially identified by an institutional electronic database. After excluding those who did not actually receive neoadjuvant therapy, were a subtype other than TNBC, and had missing receptor status or blood counts, 95 patients met eligibility for analysis. The median age of patients was 50 (range 26-79); 63 (66%) patients were treated with anthracyclines plus taxanes, 29 (31%) platinum-based chemotherapy, 2 (2%) with only anthracyclines, and 1 (1%) with only taxanes; 32 (34%) patients achieved a pCR; and 33 (35%) patients had recurrence events. Median follow up time was 47 months (range 13-123). No significant associations were found between pCR and changes in lymphocyte or monocyte count (mean lymphocyte reduction 0.74 in those with no-pCR versus 0.60 in those with pCR, p=0.30; mean monocyte reduction 0.0 in those with no-pCR versus 0.016 in those with pCR, p=0.78). There was no correlation between changes in lymphocytes or monocytes with DFS. Baseline lymphocytes or monocytes also did not correlate with pCR or DFS. Notably, there was a correlation between monocytes after neoadjuvant chemotherapy and pCR (mean monocyte level was 0.56 in those with no-pCR versus 0.46 in those with pCR, p=0.049) and DFS (median DFS in highest monocyte quartile 30 months versus in lowest quartile 107 months, p=0.022). Conclusions: Our results suggest that transient lymphopenia from chemotherapy is not associated with clinical outcomes. However, we observed lower absolute circulating monocyte counts after neoadjuvant chemotherapy were associated with better clinical outcomes. Further research assessing the role of circulating immune cells is required to understand the effects of neoadjuvant chemotherapy on clinical outcomes, which may help inform immunotherapy-based strategies. Citation Format: Talamantes SM, Costa RL, Rademaker A, Santa-Maria CA. Circulating lymphocytes and pathologic complete response rate among patients with early stage triple negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-14.

Combination chemotherapy and immunotherapy have significantly improved survival for patients with treatment-naïve advanced non-small cell lung cancer (NSCLC). We sought to evaluate the safety and efficacy of adding pembrolizumab to a standard regimen at the time of study development, nab-paclitaxel and carboplatin. Safety data from phase I have been reported, and phase II commenced with the same chemotherapy doses and flat dosing of pembrolizumab at 200 mg. Patients with treatment-naïve, stage IIIB/IV NSCLC AJCC 7 (all histology), any PDL1, no EGFR or ALK, ECOG 0-1, received carboplatin AUC 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3wks. Co-primary endpoints were progression-free survival (PFS) and response rate (RR). PDL1 was assessed prior to treatment and from biopsies obtained after cycle 4. 46 patients enrolled, 14 on phase I and 32 in phase II, from June 2015–July 2018. Accrual stopped after data was presented from similar phase III trials. 43 were evaluable for the primary endpoints. Median age was 65 years, 48% female, 45% adenocarcinoma, 94% current/former smokers, 9% brain metastases. PDL1 expression (TPS) by <1%, 1-49%, and ≥50% cutoffs was 44%, 28%, and 28%, respectively. ORR was 28%. Median PFS was 5.6 months (CI, 4.2-10.5 mo). Median OS was 15.7 mo (CI 11.1-22.3 mo). There was no statistical differences in PFS or OS outcomes by PDL1 status. Paired PDL1 results from pre- and post-treatment biopsies were available in 8 patients. PDL1 status changed categories in 4/8 samples (n=3, 0% to positive; n=1, 99% to 0%). The most common grade 3-4 adverse events (AEs) were neutropenia (64%), anemia (31%), thrombocytopenia (24%), leukopenia (16%) and fatigue (11%). Other notable AEs included rash (58%), diarrhea (47%), neuropathy (22%), arthralgia (18%), transaminitis (13%), and myalgia (11%). 18% discontinued treatment due to AEs. In an exploratory analysis, there was no difference in median PFS for those receiving total nab-paclitaxel dose of 400–799 mg/m2 compared to ≥800 mg/m2 (6.2 mo vs. 8.2 mo, p=0.62). Although the study did not meet its pre-specified endpoints of PFS 9 months and RR of 50%, results were similar to previously reported phase III Keynote 407 (squamous histology). Despite hematologic toxicity, the combination could safely be administered, and outcomes were similar for those receiving moderate doses of nab-paclitaxel compared to those with an average of at least 200 mg/m2 per cycle.

Background: Clinical trials represent a critical component in developing effective cancer therapies. Low rates of participation have negatively impacted progress in sarcoma trials. This survey study evaluated patients' attitudes, knowledge, self-efficacy for decision-making, receptivity, general willingness to participate in trials, and perceptions related to molecular profiling (MP) of tumors. Methods: IRB approval was obtained. Patients with sarcoma who were evaluated at an academic medical center between 2007 and 2017 were identified through the Enterprise Data Warehouse. A link to an online self-administered survey was emailed to patients. Data were analyzed using Spearman correlations and the Mann-Whitney test. Results: Surveys were emailed to 750 patients of which 311 patients opened and 206 patients completed a portion of the survey (27.5% of total and 66.2% of opened surveys). Of the 206 patients, median age was 52 years, 57.8% were female, and 24.8% reported metastatic disease. Greater knowledge of trials correlated with increased positive attitudes toward trial participation (p < 0.001) and positive attitudes correlated with greater trial self-efficacy (p < 0.001). Patients with metastatic disease had more positive attitudes compared with nonmetastatic (p = 0.033). Trial enrollment was associated with greater knowledge (p = 0.002) and positive attitudes (p < 0.001). Among patients who reported knowledge of tumor MP (n = 46), 30.4% credit MP with a > 50% chance of isolating a targetable result, and 71.7% assume if an experimental treatment was found based on these results, there is a > 50% likelihood of it being effective. Better attitudes and higher self-efficacy were associated with expectations of lower likelihood of developing side effects from an experimental therapy (p = 0.0096; p = 0.0184). Of patients who had MP performed (n = 18), the most important consideration for this test was its ability to improve their survival and quality of life. Conclusions: Improving knowledge of trials among sarcoma patients may lead to more positive attitudes and greater self-efficacy regarding trial enrollment. Sarcoma patients tend to overestimate the potential benefit of MP; thus, setting expectations with regards to potential benefit of MP is critically important. Legal entity responsible for the study: Northwestern University. Funding: Northwestern University. Disclosure: All authors have declared no conflicts of interest.

Background A hallmark of cancer is its ability to evade the immune system, however, it can be harnessed to detect and destroy cancer cells through inhibition of immune checkpoints such as CTLA-4 and PD-L1. This strategy has complementary and non-redundant mechanisms resulting in immune activation and antitumor synergy; progression free survival benefit has already been demonstrated in melanoma. A critical barrier in developing immunotherapies, however, is the identification of predictive biomarkers of response to therapy. Immunopharmacogenomic biomarkers, such as mutational burden, neoantigen profiles, and T cell receptor sequencing will elucidate the molecular interface between cancer and immune system, and may predict those most likely to benefit. Methods A single arm Phase II study was designed to determine the efficacy of PD-L1 and CTLA-4 inhibition and effects on immunopharmacogenomic dynamics in patients with metastatic breast cancer. The primary endpoint of this proposal is to investigate the response rate of the PD-L1 inhibitor, durvalumab, and the CTLA-4 inhibitor, tremelimumab, in metastatic breast cancer; secondary endpoints will examine the T cell receptor repertoire clonality, tumor mutational burden and neoantigen profiles. A total of 30 patients will be enrolled and treated with durvalumab 1500mg IV and tremelimumab 75mg IV monthly for 4 doses, then durvalumab 750mg every 2 weeks for 18 doses to complete 1 year of therapy with the option to renew therapy for an additional year; biopsies and blood at baseline and 2 months will be collected to assess immunopharmacogenomic biomarkers. Patients are eligible if they have triple negative or ER-positive breast cancer and have progressed on at least one line of chemotherapy and standard endocrine therapy if applicable. This is the first study to investigate immunopharmacogenomic biomarkers of response to dual checkpoint blockade in patients with metastatic breast cancer. Citation Format: Santa-Maria CA, Jain S, Flaum L, Park J-H, Kato T, Gross L, Uthe R, Tellez C, Stein R, Rademaker A, Gradishar WJ, Nakamura Y, Giles FJ, Cristofanilli M. A phase II study of PD-L1 and CTLA-4 inhibition and immunopharmcogenomics in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-01-01.

Background A hallmark of cancer is its ability to evade the immune system, however, it can be harnessed to detect and destroy cancer cells through inhibition of immune checkpoints such as CTLA-4 and PD-L1. This strategy has complementary and non-redundant mechanisms resulting in immune activation and antitumor synergy; progression free survival benefit has already been demonstrated in melanoma. A critical barrier in developing immunotherapies, however, is the identification of predictive biomarkers of response to therapy. Immunopharmacogenomic biomarkers, such as mutational burden, neoantigen profiles, and T cell receptor sequencing will elucidate the molecular interface between cancer and immune system, and may predict those most likely to benefit. Methods A single arm Phase II study was designed to determine the efficacy of PD-L1 and CTLA-4 inhibition and effects on immunopharmacogenomic dynamics in patients with metastatic breast cancer. The primary endpoint of this proposal is to investigate the response rate of the PD-L1 inhibitor, durvalumab, and the CTLA-4 inhibitor, tremelimumab, in metastatic breast cancer; secondary endpoints will examine the T cell receptor repertoire clonality, tumor mutational burden and neoantigen profiles. A total of 30 patients will be enrolled and treated with durvalumab 1500mg IV and tremelimumab 75mg IV monthly for 4 doses, then durvalumab 750mg every 2 weeks for 18 doses to complete 1 year of therapy with the option to renew therapy for an additional year; biopsies and blood at baseline and 2 months will be collected to assess immunopharmacogenomic biomarkers. Patients are eligible if they have triple negative or ER-positive breast cancer and have progressed on at least one line of chemotherapy and standard endocrine therapy if applicable. This is the first study to investigate immunopharmacogenomic biomarkers of response to dual checkpoint blockade in patients with metastatic breast cancer. Citation Format: Santa-Maria CA, Jain S, Flaum L, Park J-H, Kato T, Gross L, Uthe R, Tellez C, Stein R, Rademaker A, Gradishar WJ, Nakamura Y, Giles FJ, Cristofanilli M. A phase II study of PD-L1 and CTLA-4 inhibition and immunopharmcogenomics in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-01-01.

Background Psoriasis has been linked to increased malignancy risk, particularly lympho-haematopoietic and non-melanoma skin cancers; however, its association with cutaneous melanoma remains unclear.Objective The aim of this study was to determine if there is an association between melanoma and psoriasis in a large, urban academic population through an electronic medical record database.Methods We searched our institution's electronic medical record database (EDW-Electronic Data Warehouse) from 1/ 2001 to 11/2013. Subjects were identified by ICD-9 codes. Melanoma diagnosis was included only if documented at least 1 month after the psoriasis diagnosis was documented. Odds ratio (OR) was obtained for association between cutaneous melanoma and psoriasis. The OR was then adjusted for phototherapy and age. To minimize detection bias, we also obtained the OR for association between cutaneous melanoma and atopic dermatitis.Results We identified 10 947 patients with psoriasis, 64 of whom had a subsequent diagnosis of cutaneous melanoma. We detected a significant association between melanoma and psoriasis (OR = 1.77; 95%CI 1.38-2.26; P < 0.0001; total n = 1 525 252). After adjusting for phototherapy and age, a statistically significant association between melanoma and psoriasis remained detectable (OR = 1.9; 95%CI 1.55-2.55; P < 0.0001 and OR = 1.64; 95%CI 1.172.26; P = 0.003 respectively). The OR for melanoma with atopic dermatitis in the same patient database showed a statistically significant inverse association between the two diseases (OR = 0.35; 95%CI 0.16-0.73; P = 0.005).Conclusion Our findings show a statistically significant association between psoriasis and melanoma. After adjusting the OR for phototherapy and age, a statistically significant association remained. Further investigations exploring these associations are warranted in order to establish the relative risk for melanoma in psoriasis patients.

Lymphoma affects many young women of childbearing age. The American Society of Clinical Oncology recommends early discussion of the reproductive risks of treatment, and referral to fertility preservation (FP) specialists when appropriate (Loren et al, 2013). Women referred for FP undergo a several-step process including ovarian stimulation, oocyte retrieval, and oocyte or embryo storage (De Vos et al, 2014). Barriers to FP include poor access to reproductive specialists and concerns for treatment delay (Quinn et al, 2009, 2015). The real-world treatment delay and outcomes among female lymphoma patients attempting FP with modern techniques have not been reported previously. At our institution, practitioners are required to address fertility in all newly diagnosed cancer patients through the use of automated prompts in the electronic medical record. We have a dedicated in-house fertility preservation patient navigator (FPPN) to educate patients and expedite referrals to the reproductive specialists. We performed a retrospective chart review of lymphoma patients that contacted any fertility specialist prior to treatment at Northwestern University from 1 May 2006 until 31 August 2015. Patients who underwent FP were compared to women that contacted a FPPN but did not undergo preservation. The Northwestern University institutional review board approved the use of the clinical database for this project. Our primary objective was to assess differences in time to treatment (TTT) associated with FP. In newly diagnosed patients, TTT was defined as the time from the initial haematology consultation until the initiation of therapy. In patients with relapsed disease, TTT was defined as the time from the date of biopsy or haematology consultation until treatment initiation. Our secondary objective was to assess progression-free survival (PFS), which was defined as time from date of treatment until progression or death. The Wilcoxon rank sum test was used to compare age, TTT and follow-up time between groups. Fisher's exact test was used to compare stage, planned treatment setting, and Eastern Cooperative Oncology Group performance score (ECOG PS). Kaplan–Meier curves with the log rank test were used to compare PFS between the two groups, using a two-tailed significance level of 0·05. A total of 128 patients were identified from a fertility patient log, including 40 who underwent FP. Thirty-three of 40 patients undergoing FP and 50 of 93 patients who chose not to undergo FP were available for analysis. Reasons for exclusion included patients seen by reproductive endocrinology only and no haematologist consulted at Northwestern, lack of chemotherapy treatment records, or no treatment received following fertility contact. Pertinent baseline characteristics are outlined in Table 1. Comparing the two groups, there was a significant difference in age (P = 0·01), but not in stage (P = 0·05), planned treatment setting (P = 0·99) or ECOG PS (P = 0·99). Median follow-up was 39·3 (1·5–103·4) months, and did not differ between controls and those undergoing FP (P = 0·16). Median TTT among FP patients was 28 days overall (range: 18–76) versus 15·5 days (range: 0–74) for controls (P < 0·001; Fig 1A). Factors other than FP led to treatment delays prior to and after FP. The median time to first contact with a fertility specialist was 0 days (range −15 to +11) from haematology consultation, with several patients having contact prior to their haematology visit. The median time from oocyte retrieval until treatment initiation was 5 days (range 0–21). Seven patients had greater than 8 days from oocyte collection to treatment. The reasons were variable: 3 had delays in diagnostic work-up; 1 deferred for a trip out of town; 2 were treated subsequently at an outside institution; and 1 had follicular lymphoma with no urgency to treat. The median number of days to complete stimulation protocol was 11 (range: 5–14). A median of 14 oocytes (range: 0–37) were retrieved per patient. In 2 women, no oocytes could be successfully retrieved. Five women achieved pregnancy following FP compared to 6 controls. Of these, 3 were spontaneous and 2 required reproductive assistance, one from frozen embryos and one from frozen oocytes. Of 3 women returning to use their frozen gametes, 2 were successful and 1 was unsuccessful. Ovarian stimulation did not result in any known complications. In total, 15 patients relapsed after contacting a fertility specialist, including 7 patients in the control group and 8 in the FP arm. Patients who subsequently relapsed in both arms had high-risk features prior to fertility. There was no difference in 1-year and 5-year PFS between FP patients compared to controls (FP: 1-year PFS= 81·6%, 5-year PFS = 71·4%; Controls: 1-year PFS = 93·8%, 5-year PFS = 83·7%, P = 0·17; Fig 1B). Our study has some limitations, including those associated with a retrospective analysis. Only patients who contacted a fertility specialist were included and therefore our analysis is subject to selection bias. Our population was heterogeneous with a wide range of lymphoma subtypes, stages and treatments received. Additionally, the relatively small number of patients available for analysis limited our ability to match patients based on age, disease or prognosis, and thus there were some baseline differences between groups. However, our uniform method of referral is a major strength of our study. To our knowledge, our institution is one of the few major universities with a FPPN to centralize the collection of data on women undergoing FP, and provides a bridge between the fields of reproductive endocrinology and malignant haematology. Overall, this analysis provides important information regarding the expected delays and outcomes associated with FP. Our study demonstrates that if referral is prompt, FP contributes minimal delay to treatment and is not associated with adverse outcomes. Furthermore, it underscores the importance of access to specialists in FP and the role of the fertility navigator. Drs. Allen and Winter had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Winter, Allen, Pavone, Moravek. Acquisition, analysis, or interpretation of data: Allen, Pavone, Smith, Rafael Confino, Winter. Drafting of the manuscript: Winter, Allen. Critical revision of the manuscript for important intellectual content: Allen, Winter, Pavone, Smith, Gordon, Kazer, Lawson. Statistical analysis: Rademaker. Obtained funding: N/A. Administrative, technical, or material support: Confino, Smith. Study supervision: Winter, Pavone. The authors have no relevant conflicts of interest to disclose. This study was supported in part by research funding from the Northwestern Memorial Foundation Evergreen Grant (MEP) and the P50HD076188 Grant (partially supporting MEP and KS). N/A.

Locally advanced squamous cell carcinoma of the head and neck is commonly treated with chemoradiotherapy (CRT). It remains uncertain if residual adenopathy (RA), greater than 1 cm in maximal dimension, detected by computerized tomography following treatment has an impact on outcome. Similarly, the utility of neck dissection (ND) to pathologically evaluate RA remains undefined. We performed a retrospective analysis to assess the frequency and impact of RA and the utility of ND in SCCHN. A query of the electronic medical record using ICD9 codes was performed to identify patients that met the following inclusion criteria: age greater than 18 years, a histologically proven SCCHN diagnosed between 2003 and 2013, N1 to N3 disease, and treatment with CRT. Clinical data were abstracted through chart review. Progression free (PFS) and overall survival (OS) were estimated using Kaplan Meier analysis, and comparisons were made with log rank test. Chi-square and receiver operating characteristics were used to assess size of RA as a predictive factor. One hundred twenty three patient charts were reviewed and ninety-nine complete patient records were available for analysis. The median age at diagnosis was 56 years. Eight percent had N1 disease, 86% had N2, and 5% had N3. Following completion of CRT, 51 patients (51%) had RA. Of these, 41 patients underwent a ND, and 8 (19.5%) were found to have residual malignancy. At a median follow up of 35 months, there was no difference in PFS or OS in the patients who had radiological RA (p=0.37 and 0.72) or pathologically proven residual disease compared to those who did not. Residual adenopathy was not a predictor of residual pathologic disease. Size of RA was a poor predictor of residual cancer (AUC=0.637). Of the 48 patients tested for p16, 77% were positive by immunohistochemistry. Patients with p16 positive tumors appeared to have superior OS (p=0.038), but there was no impact on PFS (p=0.27) compared to those that were negative. Following CRT, while many patients have RA, only a small subset (19.5%) has residual active cancer. The presence of either does not impact PFS or OS. Moreover, using RA greater than 1 cm as a threshold to perform an ND lacks specificity in identifying those with pathologically positive residual cancer. These data suggest ND may be safely avoided in most patients and will help inform future prospective trials using alternative imaging modalities, such as PET/CT, to identify the subset of patients most likely to benefit from ND.

The direction of clinical research can be ascertained by reviewing ASCO Proceedings abstracts. We aimed to identify trends in HNSCC as reported in the ASCO annual meetings from 1996 to 2015 to determine whether clinical research findings lead to an improvement in patient survival. All abstracts in the head and neck section of the ASCO Proceedings from 1996 to 2015 were reviewed. Abstracts on locally advanced, recurrent, or metastatic HNSCC were further explored. Descriptive summary information was recorded regarding number of authors, randomization, trial phase, presence of novel drug or combination therapies, timing of chemotherapy, and disease-free and overall survival. From 1996 to 2015, there were a total of 2294 head and neck cancer abstracts. From 1996 to 2006, 207 abstracts were presented at the ASCO annual meeting. From 2007 to 2015, 158 abstracts were presented, of which 59 were presented at oral abstract or poster discussion sessions. The average number of authors from 1996 to 2007 was 8.82, and 10.77 from 2007 to 2015, with an average number of authors from 1996 to 2015 of 9.66. Sixty percent of studies from 1996 to 2006 focused on locally advanced disease, compared to 62% from 2007 to 2015. From 1996 to 2006, 27% were randomized studies versus 41% from 2007 to 2015. From 1996 to 2006, 57% of abstracts explored concurrent chemoradiation therapy, versus 55% of abstracts from 2006 to 2015. Fifty percent of abstracts from 1996 to 2006 investigated a novel drug or novel drug combination, compared to 95% of abstracts from 2007 to 2015. Six percent of abstracts from 1996 to 2006 demonstrated a statistically significant improvement in survival compared to 7% of abstracts from 2007 to 2015. Amongst those abstracts from 1996 to 2006, all were of patients with locally advanced disease, with the majority (7 of 12) showing a survival benefit of radiation administered with chemotherapy or cetuximab. Amongst those from 2007 to 2015, 9 or 11 were in patients with locally advanced disease. Three studies demonstrated the survival benefit of induction chemotherapy, 2 studies demonstrated the benefit of TPF versus PF, and 3 studies demonstrated the survival benefit of novel monoclonal antibodies (ie, nimotuzumab). Since 1996, the number of clinical trials of HNSCC presented at the ASCO annual meeting has increased. There has been a marked increase in the exploration of either novel drugs or novel drug combinations. This has not translated into statistically significant improvements in overall survival because most trials were nonrandomized, phase 2 studies. More randomized clinical trials are needed to build on the successes seen in the treatment of HNSCC. Novel drugs and/or drug combinations will likely lead to paradigm shifts in the treatment of human papillomavirus–positive HNSCC.

Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. How to better treat patients with unmethylated MGMT is unknown. We performed a trial combining erlotinib and bevacizumab in unmethylated GBM patients after completion of radiation (RT) and TMZ. GBM patients with an unmethylated MGMT promoter were trial eligible. Patient received standard RT (60 Gy) and TMZ (75 mg/m2 × 6 weeks) after surgical resection of their tumor. After completion of RT they started erlotinib 150 mg daily and bevacizumab 10 mg/kg every 2 weeks until progression. Imaging evaluations occurred every 8 weeks. The primary endpoint was overall survival. Of the 48 unmethylated patients enrolled, 46 were evaluable (29 men and 17 women); median age was 55.5 years (29-75) and median KPS was 90 (70-100). All patients completed RT with TMZ. The median number of cycles (1 cycle was 4 weeks) was 8 (2-47). Forty-one patients either progressed or died with a median progression free survival of 9.2 months. At a follow up of 33 months the median overall survival was 13.2 months. There were no unexpected toxicities and most observed toxicities were categorized as CTC grade 1 or 2. The combination of erlotinib and bevacizumab is tolerable but did not meet our primary endpoint of increasing survival. Importantly, more trials are needed to find better therapies for GBM patients with an unmethylated MGMT promoter.

Objectives: To determine the risk of recurrence of histologically confirmed vaginal intraepithelial neoplasia (VAIN) lesions and recurrence-free time interval based on treatment modality, histologic grade at diagnosis, and demographic characteristics.